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.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.<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.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.<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>RUNX3RUNX3F1PFH6Reactome DB_ID: 10016934nucleoplasmGENE ONTOLOGYGO:0005654UniProt:F1PFH6RUNX3Canis familiarisNCBI Taxonomy9615UniProtF1PFH61EQUAL415EQUALReactome Database ID Release 7510016934Database 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=10016934ReactomeR-CFA-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-CFA-8865393.1Reactomehttp://www.reactome.orgp-2S-SMAD3:p-2S-SMAD3:SMAD4Reactome DB_ID: 10019217F1PSQ3phospho-SMAD3p-S423,S425-SMAD3Reactome DB_ID: 9946122UniProt:F1PSQ3SMAD3UniProtF1PSQ3423EQUALO-phospho-L-serineMODMOD:00046425EQUAL1EQUAL425EQUALReactome Database ID Release 759946122Database 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=9946122ReactomeR-CFA-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-CFA-177104.12SMAD4SMAD4F1PAY5Reactome DB_ID: 9946118UniProt:F1PAY5SMAD4UniProtF1PAY51EQUAL552EQUALReactome Database ID Release 759946118Database 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=9946118ReactomeR-CFA-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-CFA-177103.11Reactome Database ID Release 7510019217Database 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=10019217ReactomeR-CFA-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-CFA-8878153.1RUNX3:p-2S-SMAD3:p-2S-SMAD3:SMAD4Reactome DB_ID: 1001921911Reactome Database ID Release 7510019219Database 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=10019219ReactomeR-CFA-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-CFA-8878146.1Reactome Database ID Release 7510019221Database 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=10019221ReactomeR-CFA-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-CFA-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.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.<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>ZFHX3ZFHX3E2RBC5Reactome DB_ID: 10019210UniProt:E2RBC5ZFHX3UniProtE2RBC51EQUAL3703EQUALReactome Database ID Release 7510019210Database 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=10019210ReactomeR-CFA-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-CFA-8878084.1RUNX3:ZFHX3Reactome DB_ID: 1001921211Reactome Database ID Release 7510019212Database 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=10019212ReactomeR-CFA-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-CFA-8878120.1Reactome Database ID Release 7510019214Database 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=10019214ReactomeR-CFA-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-CFA-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 7510019215Database 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=10019215Dimeric TGFB1Reactome DB_ID: 9945911extracellular regionGENE ONTOLOGYGO:0005576TGFB1TGFB1F1PI70Reactome DB_ID: 9945909UniProt:F1PI70TGFB1UniProtF1PI70279EQUAL390EQUALReactome Database ID Release 759945909Database 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=9945909ReactomeR-CFA-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-CFA-170838.12Reactome Database ID Release 759945911Database 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=9945911ReactomeR-CFA-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-CFA-170852.1Reactome Database ID Release 7510029615Database 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=10029615ReactomeR-CFA-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-CFA-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). In addition, RUNX3 may act as a TP53 co-factor, stimulating TP53-mediated transcription of target genes, including CDKN1A (p21) (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. 285:16693-703