BioPAX pathway converted from "PTEN Regulation" in the Reactome database. PTEN Regulation PTEN Regulation This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Regulation of PTEN gene transcription Regulation of PTEN gene transcription This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> SALL4 recruits NuRD to PTEN gene SALL4 recruits NuRD to PTEN gene This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Reactome DB_ID: 10132582 1 nucleoplasm GO 0005654 SALL4:PTEN gene [nucleoplasm] SALL4:PTEN gene Reactome DB_ID: 10099953 1 UniProt:F6X8K0 Reactome http://www.reactome.org Canis familiaris NCBI Taxonomy 9615 UniProt F6X8K0 Chain Coordinates 1 EQUAL 1053 EQUAL Reactome DB_ID: 10132580 1 Ghost homologue of PTEN gene [nucleoplasm] Ghost homologue of PTEN gene Reactome Database ID Release 83 10132582 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10132582 Reactome R-CFA-8943729 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CFA-8943729.1 Reactome DB_ID: 10048311 1 NuRD complex [nucleoplasm] NuRD complex Converted from EntitySet in Reactome Reactome DB_ID: 10048281 1 Mi-2 [nucleoplasm] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity CHD3 [nucleoplasm] CHD4 [nucleoplasm] UniProt E2RTI2 UniProt E2RHA0 Reactome DB_ID: 10048285 1 UniProt:A0A5F4CWM6 UniProt A0A5F4CWM6 1 EQUAL 291 EQUAL Converted from EntitySet in Reactome Reactome DB_ID: 10048309 1 (GATAD2A, GATAD2B) [nucleoplasm] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity Reactome DB_ID: 10048263 1 HDAC1:HDAC2 [nucleoplasm] HDAC1:HDAC2 Reactome DB_ID: 10048257 1 UniProt:J9NUI0 UniProt J9NUI0 1 EQUAL 482 EQUAL Reactome DB_ID: 10048261 1 UniProt:J9P9H5 UniProt J9P9H5 1 EQUAL 488 EQUAL Reactome Database ID Release 83 10048263 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10048263 Reactome R-CFA-4657004 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CFA-4657004.1 Reactome DB_ID: 10048271 1 UniProt:E2RM67 UniProt E2RM67 2 EQUAL 425 EQUAL Converted from EntitySet in Reactome Reactome DB_ID: 10048299 1 MTA1, MTA2, MTA3 [nucleoplasm] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity MTA1 [nucleoplasm] MTA3 [nucleoplasm] MTA2 [nucleoplasm] UniProt F1PP42 UniProt F1PXZ3 UniProt E2R655 Reactome DB_ID: 10048267 1 UniProt:A0A5F4D056 UniProt A0A5F4D056 2 EQUAL 425 EQUAL Reactome Database ID Release 83 10048311 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10048311 Reactome R-CFA-4657018 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CFA-4657018.1 Reactome DB_ID: 10132586 1 SALL4:NuRD:PTEN gene [nucleoplasm] SALL4:NuRD:PTEN gene Reactome DB_ID: 10132584 1 SALL4:NuRD [nucleoplasm] SALL4:NuRD Reactome DB_ID: 10099953 1 1 EQUAL 1053 EQUAL Reactome DB_ID: 10048311 1 Reactome Database ID Release 83 10132584 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10132584 Reactome R-CFA-8943778 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CFA-8943778.1 Reactome DB_ID: 10132580 1 Reactome Database ID Release 83 10132586 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10132586 Reactome R-CFA-8943781 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CFA-8943781.1 Reactome Database ID Release 83 10132588 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10132588 Reactome R-CFA-8943780 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CFA-8943780.1 SALL4 recruits the transcriptional repressor complex NuRD, containing histone deacetylases HDAC1 and HDAC2, to the PTEN gene promoter (Lu et al 2009, Gao et al. 2013). SALL4 may also recruit DNA methyltransferases (DNMTs) to the PTEN promoter (Yang et al. 2012). 23287862 Pubmed 2013 Targeting transcription factor SALL4 in acute myeloid leukemia by interrupting its interaction with an epigenetic complex Gao, Chong Dimitrov, Todor Yong, Kol Jia Tatetsu, Hiro Jeong, Ha-Won Luo, Hongbo R Bradner, James E Tenen, Daniel G Chai, Li Blood 121:1413-21 19440552 Pubmed 2009 Stem cell factor SALL4 represses the transcriptions of PTEN and SALL1 through an epigenetic repressor complex Lu, J Jeong, HW Kong, N Yang, Y Carroll, J Luo, HR Silberstein, LE Yupoma, LE Chai, L PLoS One 4:e5577 22128185 Pubmed 2012 Stem cell gene SALL4 suppresses transcription through recruitment of DNA methyltransferases Yang, Jianchang Corsello, Tyler R Ma, Yupo J. Biol. Chem. 287:1996-2005 inferred by electronic annotation IEA GO IEA MECOM (EVI1) recruits polycomb repressor complexes (PRCs) to the PTEN gene promoter MECOM (EVI1) recruits polycomb repressor complexes (PRCs) to the PTEN gene promoter This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Converted from EntitySet in Reactome Reactome DB_ID: 10132592 1 PRC1.4,PRC2 (EZH2) core [nucleoplasm] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity Reactome DB_ID: 10132594 1 MECOM:PTEN gene [nucleoplasm] MECOM:PTEN gene Reactome DB_ID: 10132590 1 UniProt:A0A5F4DIH5 UniProt A0A5F4DIH5 1 EQUAL 1051 EQUAL Reactome DB_ID: 10132580 1 Reactome Database ID Release 83 10132594 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10132594 Reactome R-CFA-8943810 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CFA-8943810.1 Reactome DB_ID: 10132598 1 MECOM:(PRC1.4,PRC2 (EZH2) core):PTEN gene [nucleoplasm] MECOM:(PRC1.4,PRC2 (EZH2) core):PTEN gene Reactome DB_ID: 10132596 1 MECOM:(PRC1.4,PRC2 (EZH2) core) [nucleoplasm] MECOM:(PRC1.4,PRC2 (EZH2) core) Converted from EntitySet in Reactome Reactome DB_ID: 10132592 1 Reactome DB_ID: 10132590 1 1 EQUAL 1051 EQUAL Reactome Database ID Release 83 10132596 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10132596 Reactome R-CFA-8943820 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CFA-8943820.1 Reactome DB_ID: 10132580 1 Reactome Database ID Release 83 10132598 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10132598 Reactome R-CFA-8943821 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CFA-8943821.1 Reactome Database ID Release 83 10132600 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10132600 Reactome R-CFA-8943817 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CFA-8943817.1 The transcription factor MECOM (EVI1) can associate with the polycomb repressor complexes (PRCs) and recruit them to the promoter of the PTEN gene (Song et al. 2009). Both the BMI1-containing PRC, supposedly PRC1.4, and the EZH2-containing PRC2 complex are recruited to the PTEN promoter, resulting in transcriptional silencing of the PTEN gene (Song et al. 2009, Yoshimi et al. 2011). Since the exact composition of the EZH2-containing PRC2 at the PTEN promoter is not known, the core EZH2-PRC2 complex is shown. 19884659 Pubmed 2009 The polycomb group protein Bmi-1 represses the tumor suppressor PTEN and induces epithelial-mesenchymal transition in human nasopharyngeal epithelial cells Song, Li-Bing Li, J Liao, Wen-Ting Feng, Yan Yu, Chun-Ping Hu, Li-Juan Kong, Qing-Li Xu, Li-Hua Zhang, Xing Liu, Wan-Li Li, Man-Zhi Zhang, L Kang, Tie-Bang Fu, Li-Wu Huang, Wen-Lin Xia, Yun-Fei Tsao, Sai Wah Li, Mengfeng Band, Vimla Band, Hamid Shi, Qing-Hua Zeng, Yi-Xin Zeng, Mu-Sheng J. Clin. Invest. 119:3626-36 21289308 Pubmed 2011 Evi1 represses PTEN expression and activates PI3K/AKT/mTOR via interactions with polycomb proteins Yoshimi, Akihide Goyama, Susumu Watanabe-Okochi, Naoko Yoshiki, Yumiko Nannya, Yasuhito Nitta, Eriko Arai, Shunya Sato, Tomohiko Shimabe, Munetake Nakagawa, Masahiro Imai, Yoichi Kitamura, Toshio Kurokawa, Mineo Blood 117:3617-28 inferred by electronic annotation IEA GO IEA 2.7.11.1 mTORC1 phosphorylates MAF1 mTORC1 phosphorylates MAF1 This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Reactome DB_ID: 10132707 1 cytosol GO 0005829 UniProt:A0A5F4DHS6 UniProt A0A5F4DHS6 1 EQUAL 256 EQUAL Reactome DB_ID: 113592 3 ATP(4-) [ChEBI:30616] ATP(4-) Adenosine 5'-triphosphate atp ATP ChEBI 30616 Reactome DB_ID: 29370 3 ADP(3-) [ChEBI:456216] ADP(3-) ADP trianion 5&apos;-O-[(phosphonatooxy)phosphinato]adenosine ADP ChEBI 456216 Reactome DB_ID: 10132712 1 O-phospho-L-serine at 60 (in Homo sapiens) 60 EQUAL O-phospho-L-serine [MOD:00046] O-phospho-L-serine at 68 (in Homo sapiens) 68 EQUAL O-phospho-L-serine at 75 (in Homo sapiens) 75 EQUAL 1 EQUAL 256 EQUAL PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10055322 lysosomal membrane GO 0005765 Active mTORC1 complex [lysosomal membrane] Active mTORC1 complex Reactome DB_ID: 10055320 1 mTORC1:Ragulator:RagA,B:GTP:RagC,D:GDP:SLC38A9 [lysosomal membrane] mTORC1:Ragulator:RagA,B:GTP:RagC,D:GDP:SLC38A9 Reactome DB_ID: 10055318 1 Ragulator:RagA,B:GTP:RagC,D:GDP:SLC38A9 [lysosomal membrane] Ragulator:RagA,B:GTP:RagC,D:GDP:SLC38A9 Reactome DB_ID: 10055316 1 Ragulator:RagA,B:GTP:RagC,D:GDP [lysosomal membrane] Ragulator:RagA,B:GTP:RagC,D:GDP Reactome DB_ID: 10055284 1 Ragulator [lysosomal membrane] Ragulator Reactome DB_ID: 10055282 1 UniProt:A0A5F4BTY5 UniProt A0A5F4BTY5 1 EQUAL 91 EQUAL Reactome DB_ID: 10055278 1 UniProt:F1PCV7 UniProt F1PCV7 1 EQUAL 99 EQUAL Reactome DB_ID: 10055270 1 UniProt:A0A5F4CUP6 UniProt A0A5F4CUP6 1 EQUAL 125 EQUAL Reactome DB_ID: 10055266 1 UniProt:E2QWJ8 UniProt E2QWJ8 2 EQUAL 161 EQUAL Reactome DB_ID: 10055274 1 UniProt:J9NY23 UniProt J9NY23 1 EQUAL 124 EQUAL Reactome Database ID Release 83 10055284 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10055284 Reactome R-CFA-5653921 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CFA-5653921.1 Reactome DB_ID: 10055314 1 RagA,B:GTP:RagC,D:GDP [cytosol] RagA,B:GTP:RagC,D:GDP Converted from EntitySet in Reactome Reactome DB_ID: 10055298 1 RRAGA, RRAGB:GTP [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity Converted from EntitySet in Reactome Reactome DB_ID: 10055312 1 RRAGC,RRAGD:GDP [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity Reactome Database ID Release 83 10055314 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10055314 Reactome R-CFA-5653945 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CFA-5653945.1 Reactome Database ID Release 83 10055316 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10055316 Reactome R-CFA-5653979 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CFA-5653979.1 Reactome DB_ID: 10055262 1 UniProt:F1PU20 UniProt F1PU20 1 EQUAL 561 EQUAL Reactome Database ID Release 83 10055318 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10055318 Reactome R-CFA-8952725 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CFA-8952725.1 Reactome DB_ID: 10055258 1 mTORC1 [cytosol] mTORC1 Reactome DB_ID: 10055252 1 UniProt:E2R2L2 UniProt E2R2L2 1 EQUAL 2549 EQUAL Reactome DB_ID: 10055256 1 UniProt:F1PRE6 UniProt F1PRE6 1 EQUAL 1335 EQUAL Reactome DB_ID: 10055248 1 UniProt:E2R8H1 UniProt E2R8H1 1 EQUAL 326 EQUAL Reactome Database ID Release 83 10055258 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10055258 Reactome R-CFA-377400 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CFA-377400.1 Reactome Database ID Release 83 10055320 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10055320 Reactome R-CFA-5653972 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CFA-5653972.1 Reactome DB_ID: 10055242 1 RHEB:GTP [lysosomal membrane] RHEB:GTP Reactome DB_ID: 10055238 1 UniProt:A0A5F4C7M8 UniProt A0A5F4C7M8 1 EQUAL 181 EQUAL Reactome DB_ID: 29438 1 GTP(4-) [ChEBI:37565] GTP(4-) GTP gtp guanosine 5'-triphosphate(4-) ChEBI 37565 Reactome Database ID Release 83 10055242 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10055242 Reactome R-CFA-165189 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CFA-165189.1 Reactome Database ID Release 83 10055322 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10055322 Reactome R-CFA-165678 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CFA-165678.1 GO 0004674 GO molecular function Reactome Database ID Release 83 10132713 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10132713 Reactome Database ID Release 83 10132715 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10132715 Reactome R-CFA-8944454 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CFA-8944454.1 Activated mTORC1 complex phosphorylates the transcription factor MAF1 on serine residues S60, S68 and S75 (Shor et al. 2010, Michels et al. 2010). mTORC1-mediated phosphorylation of MAF1 inhibits translocation of MAF1 to the nucleus (Shor et al. 2010). 20233713 Pubmed 2010 Requirement of the mTOR kinase for the regulation of Maf1 phosphorylation and control of RNA polymerase III-dependent transcription in cancer cells Shor, Boris Wu, Jiang Shakey, Quazi Toral-Barza, Lourdes Shi, Celine Follettie, Max Yu, Ker J. Biol. Chem. 285:15380-92 20516213 Pubmed 2010 mTORC1 directly phosphorylates and regulates human MAF1 Michels, Annemieke A Robitaille, Aaron M Buczynski-Ruchonnet, Diane Hodroj, Wassim Reina, Jaime H Hall, Michael N Hernandez, Nouria Mol. Cell. Biol. 30:3749-57 inferred by electronic annotation IEA GO IEA MAF1 translocates to the nucleus MAF1 translocates to the nucleus This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Reactome DB_ID: 10132707 1 1 EQUAL 256 EQUAL Reactome DB_ID: 10132705 1 1 EQUAL 256 EQUAL Reactome Database ID Release 83 10132717 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10132717 Reactome R-CFA-8944457 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CFA-8944457.1 Phosphorylation of MAF1 by the activated mTORC1 complex inhibits translocation of MAF1 to the nucleus, and hence its transcriptional activity, but the mechanism has not been elucidated (Shor et al. 2010). inferred by electronic annotation IEA GO IEA INHIBITION Reactome Database ID Release 83 10132718 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10132718 Reactome DB_ID: 10055322 Reactome Database ID Release 83 10145450 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10145450 Reactome R-CFA-8943724 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CFA-8943724.1 Transcription of the PTEN gene is regulated at multiple levels. Epigenetic repression involves the recruitment of Mi-2/NuRD upon SALL4 binding to the PTEN promoter (Yang et al. 2008, Lu et al. 2009) or EVI1-mediated recruitment of the polycomb repressor complex (PRC) to the PTEN promoter (Song et al. 2009, Yoshimi et al. 2011). Transcriptional regulation is also elicited by negative regulators, including NR2E1:ATN1 (atrophin-1) complex, JUN (c-Jun), SNAIL and SLUG (Zhang et al. 2006, Vasudevan et al. 2007, Escriva et al. 2008, Uygur et al. 2015) and positive regulators such as TP53 (p53), MAF1, ATF2, EGR1 or PPARG (Stambolic et al. 2001, Virolle et al. 2001, Patel et al. 2001, Shen et al. 2006, Li et al. 2016). 18172008 Pubmed 2008 Repression of PTEN phosphatase by Snail1 transcriptional factor during gamma radiation-induced apoptosis Escrivà, Maria Peiró, Sandra Herranz, Nicolás Villagrasa, Patricia Dave, Natàlia Montserrat-Sentís, Bàrbara Murray, Stephen A Francí, Clara Gridley, T Virtanen, Ismo García de Herreros, Antonio Mol. Cell. Biol. 28:1528-40 26910647 Pubmed 2016 MAF1 suppresses AKT-mTOR signaling and liver cancer through activation of PTEN transcription Li, Yue Tsang, Chi Kwan Wang, Suihai Li, Xiao-Xing Yang, Yang Fu, Liwu Huang, Wenlin Li, Ming Wang, Hui-Yun Zheng, X F Steven Hepatology 63:1928-42 11781575 Pubmed 2001 The Egr-1 transcription factor directly activates PTEN during irradiation-induced signalling Virolle, T Adamson, Eileen D Baron, V Birle, D Mercola, D Mustelin, T de Belle, I Nat. Cell Biol. 3:1124-8 25728608 Pubmed 2015 SLUG is a direct transcriptional repressor of PTEN tumor suppressor Uygur, Berna Abramo, Katrina Leikina, Evgenia Vary, Calvin Liaw, Lucy Wu, Wen-Shu Prostate 75:907-16 17974977 Pubmed 2007 Suppression of PTEN expression is essential for antiapoptosis and cellular transformation by oncogenic Ras Vasudevan, Krishna Murthi Burikhanov, Ravshan Goswami, Anindya Rangnekar, Vivek M Cancer Res. 67:10343-50 18487508 Pubmed 2008 SALL4 is a key regulator of survival and apoptosis in human leukemic cells Yang, Jianchang Chai, Li Gao, Chong Fowles, Taylor C Alipio, Zaida Dang, Hien Xu, Dan Fink, Louis M Ward, David C Ma, Yupo Blood 112:805-13 16702404 Pubmed 2006 Nuclear receptor TLX prevents retinal dystrophy and recruits the corepressor atrophin1 Zhang, Chun-Li Zou, Yuhua Yu, Ruth T Gage, Fred H Evans, Ronald M Genes Dev. 20:1308-20 16418168 Pubmed 2006 Up-regulation of PTEN (phosphatase and tensin homolog deleted on chromosome ten) mediates p38 MAPK stress signal-induced inhibition of insulin signaling. A cross-talk between stress signaling and insulin signaling in resistin-treated human endothelial cells Shen, Ying H Zhang, Lin Gan, Yehua Wang, Xinwen Wang, Jian LeMaire, Scott A Coselli, Joseph S Wang, Xing Li J. Biol. Chem. 281:7727-36 11378386 Pubmed 2001 Tumor suppressor and anti-inflammatory actions of PPARgamma agonists are mediated via upregulation of PTEN Patel, L Pass, I Coxon, P Downes, C P Smith, S A MacPhee, C H Curr. Biol. 11:764-8 11545734 Pubmed 2001 Regulation of PTEN transcription by p53 Stambolic, V MacPherson, D Sas, D Lin, Y Snow, B Jang, Y Benchimol, S Mak, T W Mol. Cell 8:317-25 inferred by electronic annotation IEA GO IEA Regulation of PTEN localization Regulation of PTEN localization This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> PTEN undergoes monoubiquitination PTEN undergoes monoubiquitination This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Reactome DB_ID: 10061842 1 UniProt:P60483 PTEN UniProt P60483 2 EQUAL 403 EQUAL Converted from EntitySet in Reactome Reactome DB_ID: 10044647 1 Ub [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity UBA52 [cytosol] UBA52(1-76) [cytosol] UBB(153-228) [cytosol] UBB(1-76) [cytosol] RPS27A(1-76) [cytosol] UBB(77-152) [cytosol] UniProt P63050 UniProt F1PEZ4 UniProt F1PDG4 UniProt A0A5F4C972 Reactome DB_ID: 10123871 1 ubiquitinylated lysine (Ub [cytosol]) at 13 (in Homo sapiens) 13 EQUAL ubiquitinylated lysine [MOD:01148] ubiquitinylated lysine (Ub [cytosol]) at 289 (in Homo sapiens) 289 EQUAL 2 EQUAL 403 EQUAL PHYSIOL-LEFT-TO-RIGHT ACTIVATION Converted from EntitySet in Reactome Reactome DB_ID: 10123879 XIAP,NEDD4 [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity GO 0061630 GO molecular function Reactome Database ID Release 83 10123880 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10123880 Reactome Database ID Release 83 10123882 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10123882 Reactome R-CFA-6807106 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CFA-6807106.1 When present at low levels in the cell, the E3 ubiquitin ligase XIAP monoubiquitinates PTEN (Van Themsche et al. 2009). NEDD4 (NEDD4-1) can also monoubiquitinate PTEN (Trotman et al. 2007). Monoubiquitination of PTEN on at least lysine residues K13 and K289 causes translocation of PTEN from the cytosol to the nucleus (Trotman et al. 2007, Van Themsche et al. 2009). 19473982 Pubmed 2009 X-linked inhibitor of apoptosis protein (XIAP) regulates PTEN ubiquitination, content, and compartmentalization Van Themsche, Céline Leblanc, Valérie Parent, Sophie Asselin, Eric J. Biol. Chem. 284:20462-6 17218261 Pubmed 2007 Ubiquitination regulates PTEN nuclear import and tumor suppression Trotman, Lloyd C Wang, Xinjiang Alimonti, Andrea Chen, Zhenbang Teruya-Feldstein, Julie Yang, Haijuan Pavletich, Nikola P Carver, Brett S Cordon-Cardo, Carlos Erdjument-Bromage, H Tempst, P Chi, Sung-Gil Kim, Hyo-Jong Misteli, Tom Jiang, Xuejun Pandolfi, Pier Paolo Cell 128:141-56 inferred by electronic annotation IEA GO IEA Monoubiquitinated PTEN translocates to the nucleus Monoubiquitinated PTEN translocates to the nucleus This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Reactome DB_ID: 10123871 1 ubiquitinylated lysine (Ub [cytosol]) at 13 (in Homo sapiens) 13 EQUAL ubiquitinylated lysine (Ub [cytosol]) at 289 (in Homo sapiens) 289 EQUAL 2 EQUAL 403 EQUAL Reactome DB_ID: 10123875 1 ubiquitinylated lysine (ubiquitin [nucleoplasm]) at 13 (in Homo sapiens) 13 EQUAL ubiquitinylated lysine (ubiquitin [nucleoplasm]) at 289 (in Homo sapiens) 289 EQUAL 2 EQUAL 403 EQUAL Reactome Database ID Release 83 10123877 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10123877 Reactome R-CFA-6807105 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CFA-6807105.1 Monoubiquitinated PTEN translocates to the nucleus. Lysine residues K13 and K289 of PTEN are important monoubiquitination targets and their mutation abrogates PTEN nuclear localization (Trotman et al. 2007). inferred by electronic annotation IEA GO IEA 3.4.19.12 USP7 deubiquitinates monoubiquitinated PTEN USP7 deubiquitinates monoubiquitinated PTEN This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Reactome DB_ID: 113518 1 water [ChEBI:15377] water ChEBI 15377 Reactome DB_ID: 10123875 1 ubiquitinylated lysine (ubiquitin [nucleoplasm]) at 13 (in Homo sapiens) 13 EQUAL ubiquitinylated lysine (ubiquitin [nucleoplasm]) at 289 (in Homo sapiens) 289 EQUAL 2 EQUAL 403 EQUAL Converted from EntitySet in Reactome Reactome DB_ID: 10044147 2 Ub [nucleoplasm] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity UBB(1-76) [nucleoplasm] UBA52 [nucleoplasm] UBA52(1-76) [nucleoplasm] UBB(153-228) [nucleoplasm] RPS27A(1-76) [nucleoplasm] UBB(77-152) [nucleoplasm] Reactome DB_ID: 10114917 1 2 EQUAL 403 EQUAL PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10100657 UniProt:F1PX83 UniProt F1PX83 1 EQUAL 1102 EQUAL GO 0004843 GO molecular function Reactome Database ID Release 83 10100686 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10100686 Reactome Database ID Release 83 10123884 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10123884 Reactome R-CFA-6807118 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CFA-6807118.1 USP7 (HAUSP) deubiquitinates monoubiquitinated nuclear PTEN, thus promoting relocalization of PTEN to the cytosol. USP7-mediated deubiquitination of PTEN is negatively regulated by PML in the presence of DAXX, but the exact mechanism has not been elucidated (Song et al. 2008). 18716620 Pubmed 2008 The deubiquitinylation and localization of PTEN are regulated by a HAUSP-PML network Song, MS Salmena, Leonardo Carracedo, Arkaitz Egia, Ainara Lo-Coco, F Teruya-Feldstein, Julie Pandolfi, Pier Paolo Nature 455:813-7 inferred by electronic annotation IEA GO IEA INHIBITION Reactome Database ID Release 83 10123885 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10123885 Reactome DB_ID: 10100332 UniProt:A0A5F4C5D6 UniProt A0A5F4C5D6 1 EQUAL 882 EQUAL Deubiquitinated PTEN translocates to the cytosol Deubiquitinated PTEN translocates to the cytosol This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Reactome DB_ID: 10114917 1 2 EQUAL 403 EQUAL Reactome DB_ID: 10061842 1 2 EQUAL 403 EQUAL Reactome Database ID Release 83 10123887 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10123887 Reactome R-CFA-6807126 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CFA-6807126.1 After nuclear monoubiquitinated PTEN gets deubiquitinated by USP7 (HAUSP), it translocates to the cytosol (Song et al. 2008). inferred by electronic annotation IEA GO IEA Reactome Database ID Release 83 10145288 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10145288 Reactome R-CFA-8948747 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CFA-8948747.1 When monoubiquitinated by E3 ubiquitin ligases XIAP and NEDD4, PTEN translocates from the cytosol to the nucleus (Trotman et al. 2007, Van Themsche et al. 2009). USP7 (HAUSP)-mediated deubiquitination of monoubiquitinated nuclear PTEN promotes relocalization of PTEN to the cytosol (Song et al. 2008). inferred by electronic annotation IEA GO IEA Regulation of PTEN stability and activity Regulation of PTEN stability and activity This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> NEDD4, WWP2, CHIP and XIAP polyubiquitinate PTEN NEDD4, WWP2, CHIP and XIAP polyubiquitinate PTEN This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Reactome DB_ID: 10061842 1 2 EQUAL 403 EQUAL Converted from EntitySet in Reactome Reactome DB_ID: 10044647 3 Reactome DB_ID: 10123890 1 ubiquitinylated lysine (polyubiquitin chain [cytosol]) at unknown position 2 EQUAL 403 EQUAL PHYSIOL-LEFT-TO-RIGHT ACTIVATION Converted from EntitySet in Reactome Reactome DB_ID: 10123896 NEDD4,STUB1,WWP2 and XIAP [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity BIRC4 [cytosol] NEDD4 [cytosol] STUB1 [cytosol] WWP2 [cytosol] UniProt Q38IV1 UniProt F1PYW3 UniProt J9NRV4 UniProt A0A5F4D937 Reactome Database ID Release 83 10123897 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10123897 Reactome Database ID Release 83 10123899 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10123899 Reactome R-CFA-6807134 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CFA-6807134.1 Several ubiquitin ligases, including NEDD4 (Wang et al. 2007), STUB1 (CHIP) (Ahmed et al. 2012), WWP2 (Maddika et al. 2011) and XIAP (Van Themsche et al. 2009) can polyubiquitinate PTEN, targeting it for degradation. 17218260 Pubmed 2007 NEDD4-1 is a proto-oncogenic ubiquitin ligase for PTEN Wang, Xinjiang Trotman, Lloyd C Koppie, Theresa Alimonti, Andrea Chen, Zhenbang Gao, Zhonghua Wang, Junru Erdjument-Bromage, H Tempst, P Cordon-Cardo, Carlos Pandolfi, Pier Paolo Jiang, Xuejun Cell 128:129-39 21532586 Pubmed 2011 WWP2 is an E3 ubiquitin ligase for PTEN Maddika, Subbareddy Kavela, Sridhar Rani, Neelam Palicharla, Vivek Reddy Pokorny, Jenny L Sarkaria, Jann N Chen, J Nat. Cell Biol. 13:728-33 22427670 Pubmed 2012 The chaperone-assisted E3 ligase C terminus of Hsc70-interacting protein (CHIP) targets PTEN for proteasomal degradation Ahmed, Syed Feroj Deb, Satamita Paul, Indranil Chatterjee, Anirban Mandal, Tapashi Chatterjee, Uttara Ghosh, Mrinal K J. Biol. Chem. 287:15996-6006 inferred by electronic annotation IEA GO IEA 2.7.11.1 AKT phosphorylates MKRN1 AKT phosphorylates MKRN1 This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Reactome DB_ID: 113592 1 Reactome DB_ID: 10082271 1 UniProt:E2RRA5 UniProt E2RRA5 1 EQUAL 482 EQUAL Reactome DB_ID: 29370 1 Reactome DB_ID: 10132889 1 O-phospho-L-serine at 109 (in Homo sapiens) 109 EQUAL 1 EQUAL 482 EQUAL PHYSIOL-LEFT-TO-RIGHT ACTIVATION Converted from EntitySet in Reactome Reactome DB_ID: 10061078 p-T,p-S-AKT [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity phospho-p-T308,S473-AKT1 [cytosol] UniProt E2RJX4 Reactome Database ID Release 83 10061079 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10061079 Reactome Database ID Release 83 10132891 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10132891 Reactome R-CFA-8948757 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CFA-8948757.1 GO 0043491 GO biological process AKT1 (and possibly AKT2 and AKT3), activated in response to EGF treatment, phosphorylates MKRN1, an E3 ubiquitin ligase, on serine residue S109. AKT-mediated phosphorylation results in stabilization of MKRN1, protecting it from ubiquitination and proteasome-mediated degradation (Lee et al. 2015). 26183061 Pubmed 2015 PI3K/AKT activation induces PTEN ubiquitination and destabilization accelerating tumourigenesis Lee, Min-Sik Jeong, Man-Hyung Lee, Hyun-Woo Han, Hyun-Ji Ko, Aram Hewitt, SM Kim, Jae-Hoon Chun, Kyung-Hee Chung, Joon-Yong Lee, Cheolju Cho, Hanbyoul Song, Jaewhan Nat Commun 6:7769 inferred by electronic annotation IEA GO IEA MKRN1 polyubiquitinates PTEN MKRN1 polyubiquitinates PTEN This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Reactome DB_ID: 10061842 1 2 EQUAL 403 EQUAL Converted from EntitySet in Reactome Reactome DB_ID: 10044647 3 Reactome DB_ID: 10123902 1 ubiquitinylated lysine (K48polyUb [cytosol]) at 289 (in Homo sapiens) 289 EQUAL 2 EQUAL 403 EQUAL PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10132889 O-phospho-L-serine at 109 (in Homo sapiens) 109 EQUAL 1 EQUAL 482 EQUAL Reactome Database ID Release 83 10132892 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10132892 Reactome Database ID Release 83 10132894 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10132894 Reactome R-CFA-8948775 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CFA-8948775.1 The C-terminal region of the E3 ubiquitin ligase MKRN1 interacts with PTEN and polyubiquitinates it on lysine residue K289, via K48 linkage. AKT-mediated phosphorylation of MKRN1 on serine residue S109 is a pre-requisite for MKRN1 stabilization and MKRN1-mediated ubiquitination of PTEN. MKRN1 is implicated as an oncogene in cervical cancer (Lee et al. 2015). inferred by electronic annotation IEA GO IEA 2.4.2.30 TNKS and TNKS2 PARylate PTEN TNKS and TNKS2 PARylate PTEN This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Reactome DB_ID: 29360 3 NAD(1-) [ChEBI:57540] NAD(1-) NAD(+) adenosine 5'-{3-[1-(3-carbamoylpyridinio)-1,4-anhydro-D-ribitol-5-yl] diphosphate} NAD anion ChEBI 57540 Reactome DB_ID: 10061842 1 2 EQUAL 403 EQUAL Reactome DB_ID: 10132896 1 adenosine diphosphoribosyl (ADP-ribosyl) modified residue at 40 (in Homo sapiens) 40 EQUAL adenosine diphosphoribosyl (ADP-ribosyl) modified residue adenosine diphosphoribosyl (ADP-ribosyl) modified residue at 150 (in Homo sapiens) 150 EQUAL adenosine diphosphoribosyl (ADP-ribosyl) modified residue at 326 (in Homo sapiens) 326 EQUAL 2 EQUAL 403 EQUAL Reactome DB_ID: 197277 3 nicotinamide [ChEBI:17154] nicotinamide ChEBI 17154 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Converted from EntitySet in Reactome Reactome DB_ID: 10102366 TNKS1/2 [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity TNKS2 [cytosol] TNKS [cytosol] UniProt F6Y5Y4 UniProt E2QU22 GO 0003950 GO molecular function Reactome Database ID Release 83 10132897 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10132897 Reactome Database ID Release 83 10132899 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10132899 Reactome R-CFA-8948800 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CFA-8948800.1 PTEN can bind tankyrases TNKS (TNKS1) and TNKS2. The interaction involves the tankyrase binding motif at the N-terminus of PTEN (RYQEDG). TNKS and TNKS2 poly-ADP-ribosylate (PARylate) PTEN on glutamic acid residues E40 and E150 and on aspartic acid residue D326. PTEN PARylation is a pre-requisite for RNF146-mediated ubiquitination of PTEN (Li et al. 2015). 25547115 Pubmed 2015 Poly-ADP ribosylation of PTEN by tankyrases promotes PTEN degradation and tumor growth Li, N Zhang, Yajie Han, Xin Liang, Ke Wang, Jiadong Feng, Lin Wang, W Songyang, Z Lin, Chunru Yang, Liuqing Yu, Yonghao Chen, J Genes Dev. 29:157-70 inferred by electronic annotation IEA GO IEA RNF146 polyubiquitinates PARylated PTEN RNF146 polyubiquitinates PARylated PTEN This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Reactome DB_ID: 10132896 1 adenosine diphosphoribosyl (ADP-ribosyl) modified residue at 40 (in Homo sapiens) 40 EQUAL adenosine diphosphoribosyl (ADP-ribosyl) modified residue at 150 (in Homo sapiens) 150 EQUAL adenosine diphosphoribosyl (ADP-ribosyl) modified residue at 326 (in Homo sapiens) 326 EQUAL 2 EQUAL 403 EQUAL Converted from EntitySet in Reactome Reactome DB_ID: 10044647 9 Reactome DB_ID: 10126656 1 adenosine diphosphoribosyl (ADP-ribosyl) modified residue at 40 (in Homo sapiens) 40 EQUAL adenosine diphosphoribosyl (ADP-ribosyl) modified residue at 150 (in Homo sapiens) 150 EQUAL adenosine diphosphoribosyl (ADP-ribosyl) modified residue at 326 (in Homo sapiens) 326 EQUAL ubiquitinylated lysine (polyubiquitin chain [cytosol]) at 342 (in Homo sapiens) 342 EQUAL ubiquitinylated lysine (polyubiquitin chain [cytosol]) at 344 (in Homo sapiens) 344 EQUAL ubiquitinylated lysine (polyubiquitin chain [cytosol]) at 349 (in Homo sapiens) 349 EQUAL 2 EQUAL 403 EQUAL PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10102346 UniProt:F1PW23 UniProt F1PW23 1 EQUAL 359 EQUAL Reactome Database ID Release 83 10132900 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10132900 Reactome Database ID Release 83 10132902 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10132902 Reactome R-CFA-8948832 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CFA-8948832.1 The E3 ubiquitin ligase RNF146 possesses a PAR recognition domain (WWE) which binds to PARylated PTEN. RNF146 polyubiquitinates PARylated PTEN, with lysine residues K342, K344 and K349 as major ubiquitination sites. RNF146-mediated ubiquitination targets PTEN for proteasome-mediated degradation (Li et al. 2015). inferred by electronic annotation IEA GO IEA Proteasome degrades polyubiquitinated PTEN Proteasome degrades polyubiquitinated PTEN This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Converted from EntitySet in Reactome Reactome DB_ID: 10126658 1 PolyUb-PTEN, K48polyUb-K289-PTEN, PolyUb-K324,K344,K349-RibC-E40,E150,D326-PTEN [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity PTEN [cytosol] phospho-PTEN [cytosol] Converted from EntitySet in Reactome Reactome DB_ID: 10044647 3 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10044755 26S proteasome [cytosol] 26S proteasome Reactome DB_ID: 10044649 1 UniProt:F1PGY4 UniProt F1PGY4 1 EQUAL 310 EQUAL Reactome DB_ID: 10044715 1 UniProt:E2RCP9 UniProt E2RCP9 1 EQUAL 908 EQUAL Reactome DB_ID: 10044727 1 Ghost homologue of PSMD6 [cytosol] Ghost homologue of PSMD6 Reactome DB_ID: 10044695 1 UniProt:E2RH48 UniProt E2RH48 1 EQUAL 418 EQUAL Reactome DB_ID: 10044729 1 UniProt:J9P6R1 UniProt J9P6R1 1 EQUAL 324 EQUAL Reactome DB_ID: 10044707 1 UniProt:E2RA22 UniProt E2RA22 1 EQUAL 226 EQUAL Reactome DB_ID: 10044741 1 UniProt:E2QT82 UniProt E2QT82 1 EQUAL 271 EQUAL Reactome DB_ID: 10044717 1 UniProt:E2QUY7 UniProt E2QUY7 1 EQUAL 534 EQUAL Reactome DB_ID: 10044697 1 UniProt:E2RM61 UniProt E2RM61 2 EQUAL 406 EQUAL Reactome DB_ID: 10044709 1 UniProt:E2RJ26 UniProt E2RJ26 2 EQUAL 422 EQUAL Reactome DB_ID: 10044731 1 Ghost homologue of PSMD8 [cytosol] Ghost homologue of PSMD8 Reactome DB_ID: 10044659 1 UniProt:E2R4H4 UniProt E2R4H4 1 EQUAL 241 EQUAL Reactome DB_ID: 10044711 1 UniProt:J9JHD9 UniProt J9JHD9 2 EQUAL 456 EQUAL Reactome DB_ID: 10044673 1 UniProt:E2QW34 UniProt E2QW34 1 EQUAL 201 EQUAL Reactome DB_ID: 10044719 1 UniProt:F1PRW0 UniProt F1PRW0 1 EQUAL 377 EQUAL Reactome DB_ID: 10044685 1 UniProt:Q5W416 PSMB8 UniProt Q5W416 73 EQUAL 276 EQUAL Reactome DB_ID: 10044689 1 UniProt:F1PQ40 UniProt F1PQ40 2 EQUAL 440 EQUAL Reactome DB_ID: 10044651 1 UniProt:A0A5F4DIX1 UniProt A0A5F4DIX1 1 EQUAL 263 EQUAL Converted from EntitySet in Reactome Reactome DB_ID: 10044703 1 Homologues of PSMC6 [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity PSMC6 [cytosol] PSMC6 [cytosol] UniProt A0A5F4C8R9 UniProt J9P1N0 Reactome DB_ID: 10044749 1 UniProt:E2RF52 UniProt E2RF52 1 EQUAL 256 EQUAL Reactome DB_ID: 10044679 1 UniProt:E2R3R2 UniProt E2R3R2 60 EQUAL 263 EQUAL Reactome DB_ID: 10044687 1 UniProt:Q5W412 PSMB9 UniProt Q5W412 21 EQUAL 219 EQUAL Reactome DB_ID: 10044667 1 UniProt:F1PUB5 UniProt F1PUB5 1 EQUAL 248 EQUAL Reactome DB_ID: 10044691 1 UniProt:F1PPH7 UniProt F1PPH7 2 EQUAL 433 EQUAL Reactome DB_ID: 10044693 1 UniProt:F1PBK7 UniProt F1PBK7 1 EQUAL 439 EQUAL Reactome DB_ID: 10044669 1 UniProt:F1PF02 UniProt F1PF02 29 EQUAL 241 EQUAL Reactome DB_ID: 10044677 1 UniProt:E2RBR6 UniProt E2RBR6 46 EQUAL 264 EQUAL Reactome DB_ID: 10044653 1 UniProt:A0A5F4CWA9 UniProt A0A5F4CWA9 2 EQUAL 234 EQUAL Reactome DB_ID: 10044739 1 Ghost homologue of PSME3 [cytosol] Ghost homologue of PSME3 Reactome DB_ID: 10044657 1 UniProt:A0A5F4C799 UniProt A0A5F4C799 1 EQUAL 261 EQUAL Reactome DB_ID: 10044737 1 UniProt:A0A5F4D079 UniProt A0A5F4D079 2 EQUAL 239 EQUAL Reactome DB_ID: 10044753 1 Ghost homologue of SEM1 [cytosol] Ghost homologue of SEM1 Converted from EntitySet in Reactome Reactome DB_ID: 10044725 1 Homologues of PSMD5 [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity PSMD5 [cytosol] PSMD5 [cytosol] UniProt J9P2T7 UniProt F1P7L2 Reactome DB_ID: 10044655 1 UniProt:J9P849 UniProt J9P849 2 EQUAL 255 EQUAL Reactome DB_ID: 10044675 1 UniProt:E2QX17 UniProt E2QX17 2 EQUAL 205 EQUAL Reactome DB_ID: 10044733 1 UniProt:E2R0R1 UniProt E2R0R1 1 EQUAL 223 EQUAL Reactome DB_ID: 10044735 1 UniProt:F6UY11 UniProt F6UY11 1 EQUAL 249 EQUAL Reactome DB_ID: 10044705 1 UniProt:A0A5F4DDS9 UniProt A0A5F4DDS9 1 EQUAL 953 EQUAL Reactome DB_ID: 10044671 1 UniProt:E2RKR9 UniProt E2RKR9 40 EQUAL 273 EQUAL Reactome DB_ID: 10044681 1 UniProt:E2R0B6 UniProt E2R0B6 35 EQUAL 239 EQUAL Converted from EntitySet in Reactome Reactome DB_ID: 10044665 1 Homologues of PSMA6 [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity PSMA6 [cytosol] PSMA6 [cytosol] UniProt A0A5F4BYV9 UniProt E2RMN2 Reactome DB_ID: 10044683 1 UniProt:A0A5F4CQX2 UniProt A0A5F4CQX2 44 EQUAL 277 EQUAL Reactome DB_ID: 10044713 1 UniProt:E2R5N5 UniProt E2R5N5 1 EQUAL 376 EQUAL Reactome DB_ID: 10044745 1 UniProt:F1PXW1 UniProt F1PXW1 1 EQUAL 1843 EQUAL Reactome DB_ID: 10044751 1 Ghost homologue of PSMB11 [cytosol] Ghost homologue of PSMB11 Reactome Database ID Release 83 10044755 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10044755 Reactome R-CFA-68819 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CFA-68819.1 GO 0004175 GO molecular function Reactome Database ID Release 83 10044756 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10044756 Reactome Database ID Release 83 10126660 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10126660 Reactome R-CFA-8850992 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CFA-8850992.1 PTEN, polyubiquitinated by either NEDD4 (Wang et al. 2007), STUB1 (CHIP) (Ahmed et al. 2011), WWP2 (Maddika et al. 2011), XIAP (Van Themsche et al. 2009), MKRN1 (Lee et al. 2015) or RNF146 (Li et al. 2015), is degraded by the proteasome. inferred by electronic annotation IEA GO IEA 3.4.19.12 USP13 and OTUD3 deubiquitinate PTEN USP13 and OTUD3 deubiquitinate PTEN This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Reactome DB_ID: 10123902 1 ubiquitinylated lysine (K48polyUb [cytosol]) at 289 (in Homo sapiens) 289 EQUAL 2 EQUAL 403 EQUAL Reactome DB_ID: 29356 1 Reactome DB_ID: 10061842 1 2 EQUAL 403 EQUAL Converted from EntitySet in Reactome Reactome DB_ID: 10044647 3 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Converted from EntitySet in Reactome Reactome DB_ID: 10123908 USP13,OTUD3 [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity USP13 [cytosol] OTUD3 [cytosol] UniProt A0A5F4DBK2 UniProt E2RLW1 Reactome Database ID Release 83 10123909 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10123909 Reactome Database ID Release 83 10123911 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10123911 Reactome R-CFA-6807206 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CFA-6807206.1 Several ubiquitin proteases deubiquitinate polyubiquitinated PTEN. USP13 and OTUD3 prolong the half-life of PTEN by preventing its proteasome-mediated degradation. Loss of USP13 or OTUD3 expression promotes AKT activation and cancer aggressiveness (Zhang et al. 2013, Yuan et al. 2015). 24270891 Pubmed 2013 Deubiquitylation and stabilization of PTEN by USP13 Zhang, Jinsong Zhang, Peijing Wei, Yongkun Piao, Hai-Long Wang, W Maddika, Subbareddy Wang, Min Chen, Dahu Sun, Yutong Hung, Mien-Chie Chen, J Ma, Li Nat. Cell Biol. 15:1486-94 26280536 Pubmed 2015 Deubiquitylase OTUD3 regulates PTEN stability and suppresses tumorigenesis Yuan, Lin Lv, Yanrong Li, Hongchang Gao, Haidong Song, Shanshan Zhang, Yuan Xing, Guichun Kong, Xiangzhen Wang, Lijing Li, Yang Zhou, Tao Gao, Daming Xiao, Zhi-Xiong Yin, Yuxin Wei, Wenyi He, Fuchu Zhang, Lingqiang Nat. Cell Biol. 17:1169-81 inferred by electronic annotation IEA GO IEA PTEN binds FRK PTEN binds FRK This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Reactome DB_ID: 10061842 1 2 EQUAL 403 EQUAL Reactome DB_ID: 10125956 1 UniProt:F1PR52 UniProt F1PR52 O4'-phospho-L-tyrosine at 387 (in Homo sapiens) 387 EQUAL O4'-phospho-L-tyrosine [MOD:00048] 1 EQUAL 505 EQUAL Reactome DB_ID: 10125958 1 PTEN:p-Y387-FRK [cytosol] PTEN:p-Y387-FRK Reactome DB_ID: 10061842 1 2 EQUAL 403 EQUAL Reactome DB_ID: 10125956 1 O4'-phospho-L-tyrosine at 387 (in Homo sapiens) 387 EQUAL 1 EQUAL 505 EQUAL Reactome Database ID Release 83 10125958 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10125958 Reactome R-CFA-8847960 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CFA-8847960.1 Reactome Database ID Release 83 10125960 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10125960 Reactome R-CFA-8847968 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CFA-8847968.1 FRK (RAK), a SRC family member kinase, binds PTEN. The interaction involves the SH3 domain of FRK and the C2 domain of PTEN (Yim et al. 2009). Like other SRC family members, FRK is autophosphorylated on a C-terminal tyrosine residue Y387. FRK possesses a nuclear localization signal and is found in both nucleus and the cytosol (Cance et al. 1994). 19345329 Pubmed 2009 Rak functions as a tumor suppressor by regulating PTEN protein stability and function Yim, Eun-Kyoung Peng, Guang Dai, Hui Hu, Ruozhen Li, Kaiyi Lu, Yiling Mills, Gordon B Meric-Bernstam, Funda Hennessy, Bryan T Craven, Rolf J Lin, Shiaw-Yih Cancer Cell 15:304-14 7696183 Pubmed 1994 Rak, a novel nuclear tyrosine kinase expressed in epithelial cells Cance, W G Craven, R J Bergman, M Xu, L Alitalo, K Liu, E T Cell Growth Differ. 5:1347-55 inferred by electronic annotation IEA GO IEA 2.7.10.2 FRK phosphorylates PTEN FRK phosphorylates PTEN This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Reactome DB_ID: 10125958 1 Reactome DB_ID: 113592 1 Reactome DB_ID: 29370 1 Reactome DB_ID: 10125963 1 O4'-phospho-L-tyrosine at 336 (in Homo sapiens) 336 EQUAL 2 EQUAL 403 EQUAL Reactome DB_ID: 10125956 1 O4'-phospho-L-tyrosine at 387 (in Homo sapiens) 387 EQUAL 1 EQUAL 505 EQUAL PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10125958 GO 0004713 GO molecular function Reactome Database ID Release 83 10125964 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10125964 Reactome Database ID Release 83 10125966 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10125966 Reactome R-CFA-8847977 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CFA-8847977.1 FRK tyrosine kinase (RAK) phosphorylates PTEN on tyrosine residue Y336. FRK-mediated phosphorylation inhibits NEDD4-mediated polyubiquitination and subsequent degradation of PTEN, thus increasing PTEN half-life. FRK-mediated phosphorylation also increases PTEN enzymatic activity (Yim et al. 2009). inferred by electronic annotation IEA GO IEA 2.7.11.1 Casein kinase II phosphorylates PTEN Casein kinase II phosphorylates PTEN This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Reactome DB_ID: 10061842 1 2 EQUAL 403 EQUAL Reactome DB_ID: 113592 5 Reactome DB_ID: 10126636 1 O-phospho-L-serine at 370 (in Homo sapiens) 370 EQUAL O-phospho-L-serine at 380 (in Homo sapiens) 380 EQUAL O-phospho-L-threonine at 382 (in Homo sapiens) 382 EQUAL O-phospho-L-threonine [MOD:00047] O-phospho-L-threonine at 383 (in Homo sapiens) 383 EQUAL O-phospho-L-serine at 385 (in Homo sapiens) 385 EQUAL 2 EQUAL 403 EQUAL Reactome DB_ID: 29370 5 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10062769 Casein kinase II [cytosol] Casein kinase II Converted from EntitySet in Reactome Reactome DB_ID: 10062767 2 CSNK2(A1:A1/A1:A2/A2:A2) [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity Reactome DB_ID: 10062751 2 UniProt:A0A5F4CFN3 UniProt A0A5F4CFN3 2 EQUAL 215 EQUAL Reactome Database ID Release 83 10062769 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10062769 Reactome R-CFA-201711 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CFA-201711.1 Reactome Database ID Release 83 10062770 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10062770 Reactome Database ID Release 83 10126638 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10126638 Reactome R-CFA-8850945 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CFA-8850945.1 Casein kinase II (CK2) constitutively phosphorylates the C-terminal tail of PTEN on serine and threonine residues S370, S380, T382, T383 and S385. S370 and S385 are the main CK2 phosphorylation sites in PTEN (Torres and Pulido 2001, Miller et al. 2002). CK2-mediated phosphorylation increases PTEN protein stability (Torres and Pulido 2001) but results in ~30% reduction in PTEN lipid phosphatase activity (Miller et al. 2002). 11035045 Pubmed 2001 The tumor suppressor PTEN is phosphorylated by the protein kinase CK2 at its C terminus. Implications for PTEN stability to proteasome-mediated degradation Torres, J Pulido, R J. Biol. Chem. 276:993-8 12297295 Pubmed 2002 Direct identification of PTEN phosphorylation sites Miller, Susan J Lou, David Y Seldin, David C Lane, William S Neel, Benjamin G FEBS Lett. 528:145-53 inferred by electronic annotation IEA GO IEA PREX2 binds PTEN and inhibits it PREX2 binds PTEN and inhibits it This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Reactome DB_ID: 10126642 1 UniProt:E2R0G2 UniProt E2R0G2 1 EQUAL 1606 EQUAL Converted from EntitySet in Reactome Reactome DB_ID: 10126644 1 PTEN, p-3S,2T-PTEN [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity phospho-PTEN [cytosol] PTEN [cytosol] Reactome DB_ID: 10126646 1 PREX2:PTEN,p-3S,2T-PTEN [cytosol] PREX2:PTEN,p-3S,2T-PTEN Reactome DB_ID: 10126642 1 1 EQUAL 1606 EQUAL Converted from EntitySet in Reactome Reactome DB_ID: 10126644 1 Reactome Database ID Release 83 10126646 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10126646 Reactome R-CFA-8850934 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CFA-8850934.1 Reactome Database ID Release 83 10126648 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10126648 Reactome R-CFA-8850961 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CFA-8850961.1 PREX2, a RAC1 guanine nucleotide exchange factor (GEF), binds to PTEN and inhibits its catalytic activity, resulting in enhanced PI3K/AKT signaling (Fine et al. 2009). The interaction involves the inositol polyphosphate 4-phosphatase domain and the pleckstrin homology (PH) domain of PREX2 and the PDZ binding domain, the phosphatase domain and the C2 domain of PTEN (Fine et al. 2009, Hodakoski et al. 2014). PREX2 binds both the unphosphorylated PTEN and PTEN phosphorylated at the C-terminal tail by casein kinase II, but inhibits the lipid phosphatase activity of phosphorylated PTEN only (Hodakoski et al. 2014). The GEF activity of PREX2 is not needed for PTEN inhibition (Fine et al. 2009).<p>PREX2 is frequently overexpressed in breast and prostate cancer (Fine et al. 2009) and mutated in melanoma (Berger et al. 2012). 19729658 Pubmed 2009 Activation of the PI3K pathway in cancer through inhibition of PTEN by exchange factor P-REX2a Fine, Barry Hodakoski, Cindy Koujak, Susan Su, Tao Saal, Lao H Maurer, Matthew Hopkins, Benjamin Keniry, Megan Sulis, ML Mense, Sarah Hibshoosh, Hanina Parsons, R Science 325:1261-5 24367090 Pubmed 2014 Regulation of PTEN inhibition by the pleckstrin homology domain of P-REX2 during insulin signaling and glucose homeostasis Hodakoski, Cindy Hopkins, Benjamin D Barrows, Douglas Mense, Sarah M Keniry, Megan Anderson, Karen E Kern, Philip A Hawkins, Phillip T Stephens, Len R Parsons, R Proc. Natl. Acad. Sci. U.S.A. 111:155-60 22622578 Pubmed 2012 Melanoma genome sequencing reveals frequent PREX2 mutations Berger, Michael F Hodis, Eran Heffernan, Timothy P Deribe, Yonathan Lissanu Lawrence, Michael S Protopopov, Alexei Ivanova, Elena Watson, Ian R Nickerson, Elizabeth Ghosh, Papia Zhang, Hailei Zeid, Rhamy Ren, Xiaojia Cibulskis, K Sivachenko, Andrey Y Wagle, Nikhil Sucker, Antje Sougnez, Carrie Onofrio, R Ambrogio, Lauren Auclair, Daniel Fennell, Timothy Carter, Scott L Drier, Yotam Stojanov, Petar Singer, Meredith A Voet, Douglas Jing, Rui Saksena, Gordon Barretina, Jordi Ramos, AH Pugh, Trevor J Stransky, N Parkin, Melissa Winckler, W Mahan, Scott Ardlie, Kristin Baldwin, Jennifer Wargo, Jennifer Schadendorf, Dirk Meyerson, M Gabriel, Stacey B Golub, Todd R Wagner, Stephan N Lander, Eric S Getz, G Chin, Lynda Garraway, Levi A Nature 485:502-6 inferred by electronic annotation IEA GO IEA TRIM27 binds PTEN TRIM27 binds PTEN This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Reactome DB_ID: 10061842 1 2 EQUAL 403 EQUAL Reactome DB_ID: 10126664 1 UniProt:F1PCA2 UniProt F1PCA2 1 EQUAL 513 EQUAL Reactome DB_ID: 10126666 1 PTEN:TRIM27 [cytosol] PTEN:TRIM27 Reactome DB_ID: 10061842 1 2 EQUAL 403 EQUAL Reactome DB_ID: 10126664 1 1 EQUAL 513 EQUAL Reactome Database ID Release 83 10126666 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10126666 Reactome R-CFA-8851000 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CFA-8851000.1 Reactome Database ID Release 83 10126668 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10126668 Reactome R-CFA-8850997 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CFA-8850997.1 TRIM27 (RFP) binds PTEN. The interaction involves the C-terminal RFP domain of TRIM27 and the C-terminal tail of PTEN (Lee et al. 2013). 23419514 Pubmed 2013 RFP-mediated ubiquitination of PTEN modulates its effect on AKT activation Lee, James T Shan, Jing Zhong, Jiayun Li, Muyang Zhou, Brenda Zhou, Amanda Parsons, R Gu, Wei Cell Res. 23:552-64 inferred by electronic annotation IEA GO IEA TRIM27 polyubiquitinates PTEN TRIM27 polyubiquitinates PTEN This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Reactome DB_ID: 10126666 1 Converted from EntitySet in Reactome Reactome DB_ID: 10044647 3 Reactome DB_ID: 10126671 1 ubiquitinylated lysine (K27polyUb [cytosol]) at unknown position 2 EQUAL 403 EQUAL Reactome DB_ID: 10126664 1 1 EQUAL 513 EQUAL PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10126666 Reactome Database ID Release 83 10126672 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10126672 Reactome Database ID Release 83 10126674 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10126674 Reactome R-CFA-8851011 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CFA-8851011.1 TRIM27 (RFP) is an E3 ubiquitin ligase for PTEN. TRIM27 polyubiquitinates PTEN on multiple lysines in the C2 domain of PTEN using K27-linkage between ubiquitin molecules. TRIM27-mediated ubiquitination inhibits PTEN lipid phosphatase activity, but does not affect PTEN protein localization or stability (Lee et al. 2013). inferred by electronic annotation IEA GO IEA Reactome Database ID Release 83 10145292 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10145292 Reactome R-CFA-8948751 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CFA-8948751.1 PTEN protein stability is regulated by ubiquitin ligases, such as NEDD4, WWP2, STUB1 (CHIP), XIAP, MKRN1 and RNF146, which polyubiquitinate PTEN in response to different stimuli and thus target it for proteasome-mediated degradation (Wang et al. 2007, Van Themsche et al. 2009, Maddika et al. 2011, Ahmed et al. 2012, Lee et al. 2015, Li et al. 2015). Several ubiquitin proteases, such as USP13 and OTUD3, can remove polyubiquitin chains from PTEN and rescue it from degradation (Zhang et al. 2013, Yuan et al. 2015). TRIM27 (RFP) is an E3 ubiquitin ligase that polyubiquitinates PTEN on multiple lysines in the C2 domain of PTEN using K27 linkage between ubiquitin molecules. TRIM27 mediated ubiquitination inhibits PTEN lipid phosphatase activity, but does not affect PTEN protein localization or stability (Lee et al. 2013).<br>PTEN phosphorylation by the tyrosine kinase FRK (RAK) inhibits NEDD4 mediated polyubiquitination and subsequent degradation of PTEN, thus increasing PTEN half life. FRK mediated phosphorylation also increases PTEN enzymatic activity (Yim et al. 2009). Casein kinase 2 (CK2) mediated phosphorylation of the C-terminus of PTEN on multiple serine and threonine residues increases PTEN protein stability (Torres and Pulido 2001) but results in ~30% reduction in PTEN lipid phosphatase activity (Miller et al. 2002).<br>PREX2, a RAC1 guanine nucleotide exchange factor (GEF) can binds to PTEN and inhibit its catalytic activity (Fine et al. 2009). inferred by electronic annotation IEA GO IEA Reactome Database ID Release 83 10145290 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10145290 Reactome R-CFA-6807070 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-CFA-6807070.1 PTEN is regulated at the level of gene transcription, mRNA translation, localization and protein stability.<p>Transcription of the PTEN gene is regulated at multiple levels. Epigenetic repression involves the recruitment of Mi-2/NuRD upon SALL4 binding to the PTEN promoter (Yang et al. 2008, Lu et al. 2009) or EVI1-mediated recruitment of the polycomb repressor complex (PRC) to the PTEN promoter (Song et al. 2009, Yoshimi et al. 2011). Transcriptional regulation is also elicited by negative regulators, including NR2E1:ATN1 (atrophin-1) complex, JUN (c-Jun), SNAIL and SLUG (Zhang et al. 2006, Vasudevan et al. 2007, Escriva et al. 2008, Uygur et al. 2015) and positive regulators such as TP53 (p53), MAF1, ATF2, EGR1 or PPARG (Stambolic et al. 2001, Virolle et al. 2001, Patel et al. 2001, Shen et al. 2006, Li et al. 2016).<p>MicroRNAs miR-26A1, miR-26A2, miR-22, miR-25, miR-302, miR-214, miR-17-5p, miR-19 and miR-205 bind PTEN mRNA and inhibit its translation into protein. These microRNAs are altered in cancer and can account for changes in PTEN levels (Meng et al. 2007, Xiao et al. 2008, Yang et al. 2008, Huse et al. 2009, Kim et al. 2010, Poliseno, Salmena, Riccardi et al. 2010, Cai et al. 2013). In addition, coding and non-coding RNAs can prevent microRNAs from binding to PTEN mRNA. These RNAs are termed competing endogenous RNAs or ceRNAs. Transcripts of the pseudogene PTENP1 and mRNAs transcribed from SERINC1, VAPA and CNOT6L genes exhibit this activity (Poliseno, Salmena, Zhang et al. 2010, Tay et al. 2011, Tay et al. 2014).<p>PTEN can translocate from the cytosol to the nucleus after undergoing monoubiquitination. PTEN's ability to localize to the nucleus contributes to its tumor suppressive role (Trotman et al. 2007). The ubiquitin protease USP7 (HAUSP) targets monoubiquitinated PTEN in the nucleus, resulting in PTEN deubiquitination and nuclear exclusion. PML, via an unknown mechanism that involves USP7- and PML-interacting protein DAXX, inhibits USP7-mediated deubiquitination of PTEN, thus promoting PTEN nuclear localization. Disruption of PML function in acute promyelocytic leukemia, through a chromosomal translocation that results in expression of a fusion protein PML-RARA, leads to aberrant PTEN localization (Song et al. 2008).<p>Several ubiquitin ligases, including NEDD4, WWP2, STUB1 (CHIP), RNF146, XIAP and MKRN1, polyubiquitinate PTEN and target it for proteasome-mediated degradation (Wang et al. 2007, Van Themsche et al. 2009, Ahmed et al. 2011, Maddika et al. 2011, Lee et al. 2015, Li et al. 2015). The ubiquitin proteases USP13 and OTUD3, frequently down-regulated in breast cancer, remove polyubiquitin chains from PTEN, thus preventing its degradation and increasing its half-life (Zhang et al. 2013, Yuan et al. 2015). The catalytic activity of PTEN is negatively regulated by PREX2 binding (Fine et al. 2009, Hodakoski et al. 2014) and TRIM27-mediated ubiquitination (Lee et al. 2013), most likely through altered PTEN conformation.<p>In addition to ubiquitination, PTEN also undergoes SUMOylation (Gonzalez-Santamaria et al. 2012, Da Silva Ferrada et al. 2013, Lang et al. 2015, Leslie et al. 2016). SUMOylation of the C2 domain of PTEN may regulate PTEN association with the plasma membrane (Shenoy et al. 2012) as well as nuclear localization of PTEN (Bassi et al. 2013, Collaud et al. 2016). PIASx-alpha, a splicing isorom of E3 SUMO-protein ligase PIAS2 has been implicated in PTEN SUMOylation (Wang et al. 2014). SUMOylation of PTEN may be regulated by activated AKT (Lin et al. 2016). Reactions describing PTEN SUMOylation will be annotated when mechanistic details become available.<p>Phosphorylation affects the stability and activity of PTEN. FRK tyrosine kinase (RAK) phosphorylates PTEN on tyrosine residue Y336, which increases PTEN half-life by inhibiting NEDD4-mediated polyubiquitination and subsequent degradation of PTEN. FRK-mediated phosphorylation also increases PTEN enzymatic activity (Yim et al. 2009). Casein kinase II (CK2) constitutively phosphorylates the C-terminal tail of PTEN on serine and threonine residues S370, S380, T382, T383 and S385. CK2-mediated phosphorylation increases PTEN protein stability (Torres and Pulido 2001) but results in ~30% reduction in PTEN lipid phosphatase activity (Miller et al. 2002).<p>PTEN localization and activity are affected by acetylation of its lysine residues (Okumura et al. 2006, Ikenoue et al. 2008, Meng et al. 2016). PTEN can undergo oxidation, which affects its function, but the mechanism is poorly understood (Tan et al. 2015, Shen et al. 2015, Verrastro et al. 2016). 22000013 Pubmed 2011 Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs Tay, Yvonne Kats, Lev Salmena, Leonardo Weiss, Dror Tan, Shen Mynn Ala, Ugo Karreth, Florian Poliseno, Laura Provero, Paolo Di Cunto, Ferdinando Lieberman, Judy Rigoutsos, Isidore Pandolfi, Pier Paolo Cell 147:344-57 23888040 Pubmed 2013 Nuclear PTEN controls DNA repair and sensitivity to genotoxic stress Bassi, C Ho, J Srikumar, T Dowling, R J O Gorrini, C Miller, S J Mak, T W Neel, B G Raught, B Stambolic, V Science 341:395-9 24344134 Pubmed 2014 PIASxα ligase enhances SUMO1 modification of PTEN protein as a SUMO E3 ligase Wang, Weibin Chen, Yifan Wang, Shuya Hu, Ningguang Cao, Zhengyi Wang, Wengong Tong, Tanjun Zhang, Xiaowei J. Biol. Chem. 289:3217-30 25867063 Pubmed 2016 SUMO modification of Akt regulates global SUMOylation and substrate SUMOylation specificity through Akt phosphorylation of Ubc9 and SUMO1 Lin, C H Liu, S Y Lee, E H Y Oncogene 35:595-607 19487573 Pubmed 2009 The PTEN-regulating microRNA miR-26a is amplified in high-grade glioma and facilitates gliomagenesis in vivo Huse, Jason T Brennan, Cameron Hambardzumyan, Dolores Wee, Boyoung Pena, John Rouhanifard, Sara H Sohn-Lee, Cherin le Sage, Carlos Agami, Reuven Tuschl, Thomas Holland, Eric C Genes Dev. 23:1327-37 20388916 Pubmed 2010 Identification of the miR-106b~25 microRNA cluster as a proto-oncogenic PTEN-targeting intron that cooperates with its host gene MCM7 in transformation Poliseno, Laura Salmena, Leonardo Riccardi, Luisa Fornari, Alessandro Song, MS Hobbs, Robin M Sportoletti, Paolo Varmeh, Shorheh Egia, Ainara Fedele, Giuseppe Rameh, Lucia Loda, Massimo Pandolfi, Pier Paolo Sci Signal 3:ra29 23073177 Pubmed 2012 Membrane association of the PTEN tumor suppressor: electrostatic interaction with phosphatidylserine-containing bilayers and regulatory role of the C-terminal tail Shenoy, Siddharth S Nanda, Hirsh Lösche, Mathias J. Struct. Biol. 180:394-408 25224693 Pubmed 2015 Analysis of PTEN ubiquitylation and SUMOylation using molecular traps Lang, Valérie Aillet, Fabienne Da Silva-Ferrada, Elisa Xolalpa, Wendy Zabaleta, Lorea Rivas, Carmen Rodriguez, Manuel S Methods 77:112-8 26561776 Pubmed 2016 Reversible oxidation of phosphatase and tensin homolog (PTEN) alters its interactions with signaling and regulatory proteins Verrastro, Ivan Tveen-Jensen, Karina Woscholski, Rudiger Spickett, Corinne M Pitt, Andrew R Free Radic. Biol. Med. 90:24-34 26862215 Pubmed 2016 The PTEN protein: cellular localization and post-translational regulation Leslie, Nick R Kriplani, Nisha Hermida, Miguel A Alvarez-Garcia, Virginia Wise, Helen M Biochem. Soc. Trans. 44:273-8 18199536 Pubmed 2008 MicroRNA expression profiling in human ovarian cancer: miR-214 induces cell survival and cisplatin resistance by targeting PTEN Yang, Hua Kong, William He, Lili Zhao, Jian-Jun O'Donnell, Joshua D Wang, Jiawang Wenham, Robert M Coppola, Domenico Kruk, Patricia A Nicosia, Santo V Cheng, Jin Q Cancer Res. 68:425-33 17681183 Pubmed 2007 MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer Meng, Fanyin Henson, Roger Wehbe-Janek, Hania Ghoshal, Kalpana Jacob, Samson T Patel, Tushar Gastroenterology 133:647-58 23856247 Pubmed 2013 miR-205 targets PTEN and PHLPP2 to augment AKT signaling and drive malignant phenotypes in non-small cell lung cancer Cai, Junchao Fang, Lishan Huang, Yongbo Li, Rong Yuan, Jie Yang, Y Zhu, Xun Chen, Baixue Wu, Jueheng Li, Mengfeng Cancer Res. 73:5402-15 20577206 Pubmed 2010 A coding-independent function of gene and pseudogene mRNAs regulates tumour biology Poliseno, Laura Salmena, Leonardo Zhang, Jiangwen Carver, Brett Haveman, William J Pandolfi, Pier Paolo Nature 465:1033-8 26279303 Pubmed 2016 PTEN activation through K163 acetylation by inhibiting HDAC6 contributes to tumour inhibition Meng, Z Jia, L-F Gan, Y-H Oncogene 35:2333-44 16829519 Pubmed 2006 PCAF modulates PTEN activity Okumura, Koichi Mendoza, Michelle Bachoo, Robert M DePinho, Ronald A Cavenee, Webster K Furnari, Frank B J. Biol. Chem. 281:26562-8 23604351 Pubmed 2013 Analysis of SUMOylated proteins using SUMO-traps Da Silva-Ferrada, Elisa Xolalpa, Wendy Lang, Valérie Aillet, Fabienne Martin-Ruiz, Itziar de la Cruz-Herrera, Carlos F Lopitz-Otsoa, Fernando Carracedo, Arkaitz Goldenberg, SJ Rivas, Carmen England, Patrick Rodriguez, Manuel S Sci Rep 3:1690 18757404 Pubmed 2008 PTEN acetylation modulates its interaction with PDZ domain Ikenoue, T Inoki, Ken Zhao, B Guan, KL Cancer Res. 68:6908-12 20080666 Pubmed 2010 Integrative genome analysis reveals an oncomir/oncogene cluster regulating glioblastoma survivorship Kim, Hyunsoo Huang, Wei Jiang, Xiuli Pennicooke, Brenton Park, Peter J Johnson, Mark D Proc. Natl. Acad. Sci. U.S.A. 107:2183-8 25737250 Pubmed 2015 Differential thiol oxidation of the signaling proteins Akt, PTEN or PP2A determines whether Akt phosphorylation is enhanced or inhibited by oxidative stress in C2C12 myotubes derived from skeletal muscle Tan, Pearl Lin Shavlakadze, Tea Grounds, Miranda D Arthur, Peter G Int. J. Biochem. Cell Biol. 62:72-9 26415504 Pubmed 2015 AIF inhibits tumor metastasis by protecting PTEN from oxidation Shen, Shao-Ming Guo, Meng Xiong, Zhong Yu, Yun Zhao, Xu-Yun Zhang, Fei-Fei Chen, Guo-Qiang EMBO Rep. 16:1563-80 18327259 Pubmed 2008 Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes Xiao, Changchun Srinivasan, Lakshmi Calado, Dinis Pedro Patterson, Heide Christine Zhang, Baochun Wang, Jing Henderson, Joel M Kutok, Jeffrey L Rajewsky, Klaus Nat. Immunol. 9:405-14 23013792 Pubmed 2012 Regulation of the tumor suppressor PTEN by SUMO González-Santamaría, J Campagna, M Ortega-Molina, A Marcos-Villar, L de la Cruz-Herrera, C F González, D Gallego, P Lopitz-Otsoa, F Esteban, M Rodriguez, M S Serrano, M Rivas, C Cell Death Dis 3:e393 25884169 Pubmed 2015 Lung neuroendocrine tumors: correlation of ubiquitinylation and sumoylation with nucleo-cytosolic partitioning of PTEN Collaud, Stéphane Tischler, Verena Atanassoff, Andrej Wiedl, Thomas Komminoth, Paul Oehlschlegel, Christian Weder, Walter Soltermann, A BMC Cancer 15:74 24429633 Pubmed 2014 The multilayered complexity of ceRNA crosstalk and competition Tay, Yvonne Rinn, John Pandolfi, Pier Paolo Nature 505:344-52 inferred by electronic annotation IEA GO IEA