BioPAX pathway converted from "RUNX3 regulates CDKN1A transcription" in the Reactome database.RUNX3 regulates CDKN1A transcriptionThis 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>LEFT-TO-RIGHTRUNX3 binds SMAD3 and SMAD4This 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>Runx3RUNX3A0A0G2K9V0Reactome DB_ID: 9916437nucleoplasmGENE ONTOLOGYGO:0005654UniProt:A0A0G2K9V0Runx3Rattus norvegicusNCBI Taxonomy10116UniProtA0A0G2K9V01EQUAL415EQUALReactome Database ID Release 759916437Database 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=9916437ReactomeR-RNO-88653931Reactome 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-RNO-8865393.1Reactomehttp://www.reactome.orgp-2S-SMAD3:p-2S-SMAD3:SMAD4Reactome DB_ID: 9918998Smad4SMAD4O70437Reactome DB_ID: 9835009UniProt:O70437Smad4UniProtO704371EQUAL552EQUALReactome Database ID Release 759835009Database 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=9835009ReactomeR-RNO-1771031Reactome 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-RNO-177103.11P84025phospho-Smad3p-S423,S425-SMAD3Reactome DB_ID: 9835013UniProt:P84025Smad3UniProtP84025423EQUALO-phospho-L-serineMODMOD:00046425EQUAL1EQUAL425EQUALReactome Database ID Release 759835013Database 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=9835013ReactomeR-RNO-1771041Reactome 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-RNO-177104.12Reactome Database ID Release 759918998Database 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=9918998ReactomeR-RNO-88781531Reactome 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-RNO-8878153.1RUNX3:p-2S-SMAD3:p-2S-SMAD3:SMAD4Reactome DB_ID: 991900011Reactome Database ID Release 759919000Database 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=9919000ReactomeR-RNO-88781461Reactome 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-RNO-8878146.1Reactome Database ID Release 759919002Database 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=9919002ReactomeR-RNO-88781431Reactome 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-RNO-8878143.1RUNX3 binds the complex of SMAD3 and SMAD4, formed in response to TGF-beta (TGFB1) signaling (Hanai et al. 1999, Chi et al. 2005).10531362Pubmed1999Interaction and functional cooperation of PEBP2/CBF with Smads. Synergistic induction of the immunoglobulin germline Calpha promoterHanai, JChen, L FKanno, TOhtani-Fujita, NKim, W YGuo, W HImamura, TIshidou, YFukuchi, MShi, M JStavnezer, JKawabata, MMiyazono, KIto, YJ. Biol. Chem. 274:31577-8216135801Pubmed2005RUNX3 suppresses gastric epithelial cell growth by inducing p21(WAF1/Cip1) expression in cooperation with transforming growth factor {beta}-activated SMADChi, Xin-ZiYang, Jeung-OokLee, Kwang-YoulIto, KoseiSakakura, ChoheiLi, Qing-LinKim, Hye-RyunCha, Eun-JeungLee, Yong-HeeKaneda, AtsushiUshijima, ToshikazuKim, Wun-JaeIto, YoshiakiBae, Suk-ChulMol. Cell. Biol. 25:8097-107inferred from electronic annotationEVIDENCE CODEECO:0000203LEFT-TO-RIGHTRUNX3 binds ZFHX3This 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>Zfhx3ZFHX3F1M4Q6Reactome DB_ID: 9918991UniProt:F1M4Q6Zfhx3UniProtF1M4Q61EQUAL3703EQUALReactome Database ID Release 759918991Database 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=9918991ReactomeR-RNO-88780841Reactome 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-RNO-8878084.1RUNX3:ZFHX3Reactome DB_ID: 991899311Reactome Database ID Release 759918993Database 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=9918993ReactomeR-RNO-88781201Reactome 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-RNO-8878120.1Reactome Database ID Release 759918995Database 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=9918995ReactomeR-RNO-88781171Reactome 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-RNO-8878117.1In response to TGF-beta (TGFB1) signaling, RUNX3 binds to the homeobox transcription factor and tumor suppressor ZFHX3 (ATBF1). The exact mechanism and regulation of RUNX3 and ATBF1 binding is not known (Mabuchi et al. 2010).20599712Pubmed2010Tumor suppressor, AT motif binding factor 1 (ATBF1), translocates to the nucleus with runt domain transcription factor 3 (RUNX3) in response to TGF-beta signal transductionMabuchi, MotoshiKataoka, HiromiMiura, YutakaKim, Tae-SunKawaguchi, MakotoEbi, MasahideTanaka, MamoruMori, YoshinoriKubota, EijiMizushima, TakashiShimura, TakayaMizoshita, TsutomuTanida, SatoshiKamiya, TakeshiAsai, KJoh, TakashiBiochem. Biophys. Res. Commun. 398:321-5ACTIVATIONReactome Database ID Release 759918996Database 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=9918996Dimeric TGFB1Reactome DB_ID: 9834790extracellular regionGENE ONTOLOGYGO:0005576Tgfb1TGFB1P17246Reactome DB_ID: 9834788UniProt:P17246Tgfb1UniProtP17246279EQUAL390EQUALReactome Database ID Release 759834788Database 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=9834788ReactomeR-RNO-1708381Reactome 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-RNO-170838.12Reactome Database ID Release 759834790Database 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=9834790ReactomeR-RNO-1708521Reactome 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-RNO-170852.1LEFT-TO-RIGHTRUNX3 binds TP53This 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>TP53 TetramerReactome DB_ID: 9886947Tp53TP53P10361Reactome DB_ID: 9886314UniProt:P10361Tp53UniProtP103611EQUAL393EQUALReactome Database ID Release 759886314Database 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=9886314ReactomeR-RNO-694881Reactome 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-RNO-69488.14Reactome Database ID Release 759886947Database 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=9886947ReactomeR-RNO-32091941Reactome 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-RNO-3209194.1RUNX3:TP53 tetramerReactome DB_ID: 992157911Reactome Database ID Release 759921579Database 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=9921579ReactomeR-RNO-89521231Reactome 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-RNO-8952123.1Reactome Database ID Release 759921581Database 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=9921581ReactomeR-RNO-89521281Reactome 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-RNO-8952128.1RUNX3 can bind to TP53 (p53). The interaction involves the C-termini of both RUNX3 and TP53. RUNX3 may act as a TP53 co-factor, stimulating TP53-mediated transcription of target genes, including CDKN1A (p21). RUNX3 may also interact with phosphorylated ATM kinase in response to DNA damage and facilitate ATM-mediated phosphorylation and stabilization of TP53 (Yamada et al. 2010).20353948Pubmed2010RUNX3 modulates DNA damage-mediated phosphorylation of tumor suppressor p53 at Ser-15 and acts as a co-activator for p53Yamada, ChizuOzaki, ToshinoriAndo, KSuenaga, YusukeInoue, Ken-ichiIto, YoshiakiOkoshi, RintaroKageyama, HajimeKimura, HidekiMiyazaki, MasaruNakagawara, AkiraJ. Biol. Chem. 285:16693-703Reactome Database ID Release 759930524Database 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=9930524ReactomeR-RNO-89418551Reactome 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-RNO-8941855.1RUNX3 contributes to the upregulation of the CDKN1A (p21) gene transcription in response to TGF-beta (TGFB1) signaling. RUNX3 binds to SMAD3 and SMAD4, and cooperates with the activated SMAD3:SMAD4 complex in transactivation of CDKN1A. Runx3 knockout mice exhibit decreased sensitivity to TGF-beta and develop gastric epithelial hyperplasia (Chi et al. 2005). In response to TGF-beta signaling, the CBFB:RUNX3 complex binds to the tumor suppressor ZFHX3 (ATBF1) and, through an unknown mechanism, this complex positively regulates the CDKN1A transcription (Mabuchi et al. 2010).<br>In addition, RUNX3 may act as a TP53 co-factor, stimulating TP53-mediated transcription of target genes, including CDKN1A (p21) (Yamada et al. 2010).