Transcriptional regulation by RUNX3 (Homo sapiens)

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13, 16, 18, 19, 24...50, 5535, 84, 1045710883827179, 8359258988335, 84, 10479, 83567412, 47, 11110, 12, 17, 21, 47...218310923, 825811, 42, 69, 1071088810879257433, 51836, 8398827142, 50566, 8321, 33, 51827, 7832, 7427, 78109cytosolnucleoplasmBRD2 CDKN1A geneH2OSMURF1 UBC(533-608) RUNX1 geneUBC(457-532) EP300 RUNX3:p-2S-SMAD3:p-2S-SMAD3:SMAD4:CDKN1A geneHES1RUNX3:p-2S-SMAD3:p-2S-SMAD3:SMAD4Ac-K94,K171-RUNX3:CBFB:EP300PSMD12 CREBBP CCND1 gene RUNX3 UBB(153-228) MAML2 Ac-K94,K171-RUNX3 SNW1 ZFHX3SMURF2 CBFB TEAD4 RUNX3:CBFB:CCND1:HDAC4CCND1UBB(77-152) MYC genePSMC6 PSMB10 TCF7L1 LEF1 RBPJ MAML1 JAG1EP300 PSMF1 WWTR1 HDAC4 RUNX3:TCF7L2,(LEF1,TCF7L1)CTGF geneCTNNB1 TCF7L1 TEAD2 MAML3 BRD2 PSMA6 PSME2 PSMD9 RUNX3 TEAD3 RUNX3 CBFB PSMD8 TEAD1 TEAD2 ITGAL,(ITGA4)CBFB UBA52(1-76) HES1 gene RUNX3 CTNNB1:TCF7L2,LEF1:CCND1 GeneUBC(153-228) RUNX3 LEF1 EP300 PSMC3 PSMB8 CBFBUBA52(1-76) p-S423,S425-SMAD3 KAT2A MAML1 LEF1 SHFM1 MyrG-p-Y419-SRC UBC(229-304) RUNX3:CBFBRUNX3:CTNNB1:TCF7L2,(LEF1,TCF7L1,TCF7)SNW1 TCF7L2 RUNX3 UBC(1-76) MAMLD1 TEAD3 MAML1 PSMD10 YAP1:TEAD1,TEAD4,(TEAD2,TEAD3)UBC(381-456) MAML2 RORC gene UBC(77-152) CCND1 NICD1 CoA-SHCTNNB1 PSMB7 MyrG-p-Y419-SRC:RUNX3RUNX1 Ac-CoARUNX3 RUNX1 CBFB CDKN1APSMD6 UBB(153-228) BCL2L11 geneCTNNB1:TCF7L2,(LEF1,TCF7L1,TCF7)YAP1 TCF7L2 CREBBP MAML2 TEAD4 PSMD2 CBFB CDKN1A gene HDAC4 RBPJ CBFB TEAD2 NOTCH1 CoactivatorComplexUBC(153-228) RPS27A(1-76) PSMB6 RORC geneITGAL gene,(ITGA4gene)p-S166,S188-MDM2 ITGA4 Ac-K94,K171-RUNX3 RUNX3:YAP1:TEAD1,TEAD4,(TEAD2,TEAD3)HES1 gene CTNNB1 p-S423,S425-SMAD3 RUNX3 Dimeric TGFB1p-2S-SMAD3:p-2S-SMAD3:SMAD4BRD2 Ac-K94,K171-RUNX3 PSMD13 MAMLD1 Ac-K94,K171-RUNX3 CTGFCBFB RUNX3:CBFB:ITGALgene,(ITGA4 gene)KAT2A RUNX3 KRAS:GTPUBB(1-76) CBFB BRD2 PSMD11 TEADs:YAP1UBC(305-380) NOTCH1 CoactivatorComplex:HES1 GeneMyrG-p-Y419-SRCSignaling byTGF-beta ReceptorComplexPSMC1 YAP1 TEAD1 BRD2 UBC(77-152) LEF1 CDKN2A gene RUNX1 gene EP300TCF7L2 RUNX3 p-S423,S425-SMAD3 CH3COO-TCF7L1 RUNX3 FOXO3 Ac-K94,K171-RUNX3 SPP1RUNX3:JAG1 geneTCF7L2 UBC(533-608) PSMB3 PSMA1 PSMC4 PSMD5 ITGA4 gene PSMB2 CTNNB1:TCF7L2,LEF1TP53 BCL2L11UBC(457-532) NICD1 CCND1 RUNX3 TEAD2 TCF7L1 CTNNB1 EP300MAMLD1 TP53 TetramerTEAD2 RUNX3 ITGAL gene TEAD4 RUNX1:CBFB,(Ac-K94,K171-RUNX3:CBFB:EP300:BRD2):CDKN2A geneCBFB PSMA5 PSMD4 PolyUb-RUNX3RUNX3 RUNX3:ZFHX3HES1 geneCBFB UBC(229-304) UBC(305-380) ADPp-Y-RUNX3KAT2B PSMA2 PSME3 LEF1 TCF7L2 KRAS UBC(381-456) PolyUb-K94,K148-RUNX3PSMA3 LEF1 UBB(77-152) MAML3 JAG1 geneEP300 MAML3 RORC-2KAT2A UBC(609-684) RUNX3 CDKN2A geneTP53 RUNX3:CBFB:RUNX1geneKAT2B EP300 TCF7L1/TCF7L2/LEF1:CTNNB1RUNX3:TP53 tetramerTEAD1 RUNX3 SNW1 NICD1 LEF1 TEAD3 PSMB4 PSMA7 TCF7L1/TCF7L2/LEF1:CTNNB1:MYC geneTEAD4 p14-ARFUBC(609-684) CREBBP HDAC4ATPp14-ARF mRNATCF7L2 RUNX3:CTNNB1:TCF7L2,(LEF1)TCF7L2 SMAD4 PSMB1 PSME1 PSMA4 UbKAT2A RUNX1 mRNASNW1 Ac-K94,K171-RUNX3:CBFB:BRD2:CCND1:HDAC4CTNNB1 RBPJ BRD2 Ac-K94,K171-RUNX3:CBFB:EP300:BRD2GTP CCND1 TEAD3 EP300 RPS27A(1-76) CREBBP RUNX3CTNNB1 PSMD14 CTGF gene EP300 UBC(1-76) PSMD1 SMAD4 SPP1 geneCBFB PolyUb-K94,K148-RUNX3RUNX3:CBFB:EP300TEADs:YAP1:CTGF geneRUNX1:CBFB,(Ac-K94,K171-RUNX3:CBFB:EP300:BRD2)RUNX3:CBFB:RORC geneTEAD:WWTR1(TAZ)YAP1 KAT2B TEAD1 PSMC2 RUNX3 CBFB TGFB1 PSMD7 TEAD4 ITGAL RUNX3 MAML1 JAG1 gene ITGAL gene CCND1CCND1 geneLEF1 RUNX3:p-2S-SMAD3:p-2S-SMAD3:SMAD4:FOXO3:BCL2L11 geneRUNX3 RUNX3UBB(1-76) PSMB5 RUNX3:NOTCH1coactivatorcomplex:HES1 geneFOXO3p-S166,S188-MDM2dimerTEAD1 MAML3 ITGA4 gene MAML2 PSMC5 TCF7 RUNX3 SMAD4 PSMD3 EP300 MAMLD1 UbPSMB9 YAP1 SMAD4 TCF7 26S proteasomeMYCNICD1 Signaling by NOTCH1BRD2 homodimerSMURFMYC gene ZFHX3 BCL2L11 gene TCF7L2 RBPJ EP300 KAT2B p-S423,S425-SMAD3 TCF7L1 RUNX3:NOTCH1Coactivator ComplexTEAD3 RUNX3:p-S166,S188-MDM2 dimerAc-K94,K171-RUNX3 p-S166,S188-MDM2 Ac-K94,K171-RUNX3:CBFB:BRD2:CCND18245, 978321831082533, 5127835726591-3, 5, 7...49750, 55215610881097174836, 8333, 5198748369, 10736


Description

The transcription factor RUNX3 is a RUNX family member. All RUNX family members, RUNX1, RUNX2 and RUNX3, possess a highly conserved Runt domain, involved in DNA binding. For a more detailed description of the structure of RUNX proteins, please refer to the pathway 'Transcriptional regulation by RUNX1'. Similar to RUNX1 and RUNX2, RUNX3 forms a transcriptionally active heterodimer with CBFB (CBF-beta). Studies in mice have shown that RUNX3 plays a role in neurogenesis and development of T lymphocytes. RUNX3 is implicated as a tumor suppressor gene in various human malignancies.
During nervous system formation, the Cbfb:Runx3 complex is involved in development of mouse proprioceptive dorsal root ganglion neurons by regulating expression of Ntrk3 (Neurotrophic tyrosine kinase receptor type 3) and possibly other genes (Inoue et al. 2002, Kramer et al. 2006, Nakamura et al. 2008, Dykes et al. 2011, Ogihara et al. 2016). It is not yet known whether RUNX3 is involved in human neuronal development and neuronal disorders.
RUNX3 plays a major role in immune response. RUNX3 regulates development of T lymphocytes. In mouse hematopoietic stem cells, expression of Runx3 is regulated by the transcription factor TAL1 (Landry et al. 2008). RUNX3 promotes the CD8+ lineage fate in developing thymocytes. In the CD4+ thymocyte lineage in mice, the transcription factor ThPOK induces transcription of SOCS family members, which repress Runx3 expression (Luckey et al. 2014). RUNX3, along with RUNX1 and ETS1, is implicated in regulation of transcription of the CD6 gene, encoding a lymphocyte surface receptor expressed on developing and mature T cells (Arman et al. 2009). RUNX3 and ThPOK regulate intestinal CD4+ T cell immunity in a TGF-beta and retinoic acid-dependent manner, which is important for cellular defense against intestinal pathogens (Reis et al. 2013). Besides T lymphocytes, RUNX3 is a key transcription factor in the commitment of innate lymphoid cells ILC1 and ILC3 (Ebihara et al. 2015). RUNX3 regulates expression of CD11A and CD49D integrin genes, involved in immune and inflammatory responses (Dominguez-Soto et al. 2005). RUNX3 is involved in mouse TGF-beta-mediated dendritic cell function and its deficiency is linked to airway inflammation (Fainaru et al. 2004).
In addition to its developmental role, RUNX3 is implicated as a tumor suppressor. The loss of RUNX3 expression and function was first causally linked to the genesis and progression of human gastric cancer (Li et al. 2002). Expression of RUNX3 increases in human pancreatic islet of Langerhans cells but not in pancreatic adenocarcinoma cells in response to differentiation stimulus (serum withdrawal) (Levkovitz et al. 2010). Hypermethylation of the RUNX3 gene is associated with an increased risk for progression of Barrett's esophagus to esophageal adenocarcinoma (Schulmann et al. 2005). Hypermethylation-mediated silencing of the RUNX3 gene expression is also frequent in granulosa cell tumors (Dhillon et al. 2004) and has also been reported in colon cancer (Weisenberger et al. 2006), breast cancer (Lau et al. 2006, Huang et al. 2012), bladder cancer (Wolff et al. 2008) and gastric cancer (Li et al. 2002). In colorectal cancer, RUNX3 is one of the five markers in a gene panel used to classify CpG island methylator phenotype (CIMP+) (Weisenberger et al. 2006).
RUNX3 and CBFB are frequently downregulated in gastric cancer. RUNX3 cooperates with TGF-beta to maintain homeostasis in the stomach and is involved in TGF-beta-induced cell cycle arrest of stomach epithelial cells. Runx3 knockout mice exhibit decreased sensitivity to TGF-beta and develop gastric epithelial hyperplasia (Li et al. 2002, Chi et al. 2005). RUNX3-mediated inhibition of binding of TEADs:YAP1 complexes to target promoters is also implicated in gastric cancer suppression (Qiao et al. 2016).
RUNX3 is a negative regulator of NOTCH signaling and RUNX3-mediated inhibition of NOTCH activity may play a tumor suppressor role in hepatocellular carcinoma (Gao et al. 2010, Nishina et al. 2011).
In addition to RUNX3 silencing through promoter hypermethylation in breast cancer (Lau et al. 2006), Runx3+/- mice are predisposed to breast cancer development. RUNX3 downregulates estrogen receptor alpha (ESR1) protein levels in a proteasome-dependent manner (Huang et al. 2012).
Besides its tumor suppressor role, mainly manifested through its negative effect on cell proliferation, RUNX3 can promote cancer cell invasion by stimulating expression of genes involved in metastasis, such as osteopontin (SPP1) (Whittle et al. 2015). View original pathway at:Reactome.

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Reactome-Converter 
Pathway is converted from Reactome ID: 8878159
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Reactome version: 66
Reactome Author 
Reactome Author: Orlic-Milacic, Marija

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Bibliography

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  68. van Tetering G, van Diest P, Verlaan I, van der Wall E, Kopan R, Vooijs M.; ''Metalloprotease ADAM10 is required for Notch1 site 2 cleavage.''; PubMed Europe PMC
  69. Chan SW, Lim CJ, Loo LS, Chong YF, Huang C, Hong W.; ''TEADs mediate nuclear retention of TAZ to promote oncogenic transformation.''; PubMed Europe PMC
  70. Schulmann K, Sterian A, Berki A, Yin J, Sato F, Xu Y, Olaru A, Wang S, Mori Y, Deacu E, Hamilton J, Kan T, Krasna MJ, Beer DG, Pepe MS, Abraham JM, Feng Z, Schmiegel W, Greenwald BD, Meltzer SJ.; ''Inactivation of p16, RUNX3, and HPP1 occurs early in Barrett's-associated neoplastic progression and predicts progression risk.''; PubMed Europe PMC
  71. Spender LC, Whiteman HJ, Karstegl CE, Farrell PJ.; ''Transcriptional cross-regulation of RUNX1 by RUNX3 in human B cells.''; PubMed Europe PMC
  72. Levkovitz L, Yosef N, Gershengorn MC, Ruppin E, Sharan R, Oron Y.; ''A novel HMM-based method for detecting enriched transcription factor binding sites reveals RUNX3 as a potential target in pancreatic cancer biology.''; PubMed Europe PMC
  73. Huang B, Qu Z, Ong CW, Tsang YH, Xiao G, Shapiro D, Salto-Tellez M, Ito K, Ito Y, Chen LF.; ''RUNX3 acts as a tumor suppressor in breast cancer by targeting estrogen receptor α.''; PubMed Europe PMC
  74. Chi XZ, Yang JO, Lee KY, Ito K, Sakakura C, Li QL, Kim HR, Cha EJ, Lee YH, Kaneda A, Ushijima T, Kim WJ, Ito Y, Bae SC.; ''RUNX3 suppresses gastric epithelial cell growth by inducing p21(WAF1/Cip1) expression in cooperation with transforming growth factor {beta}-activated SMAD.''; PubMed Europe PMC
  75. Luo B, Aster JC, Hasserjian RP, Kuo F, Sklar J.; ''Isolation and functional analysis of a cDNA for human Jagged2, a gene encoding a ligand for the Notch1 receptor.''; PubMed Europe PMC
  76. Dhillon VS, Shahid M, Husain SA.; ''CpG methylation of the FHIT, FANCF, cyclin-D2, BRCA2 and RUNX3 genes in Granulosa cell tumors (GCTs) of ovarian origin.''; PubMed Europe PMC
  77. Fainaru O, Woolf E, Lotem J, Yarmus M, Brenner O, Goldenberg D, Negreanu V, Bernstein Y, Levanon D, Jung S, Groner Y.; ''Runx3 regulates mouse TGF-beta-mediated dendritic cell function and its absence results in airway inflammation.''; PubMed Europe PMC
  78. Domínguez-Soto A, Relloso M, Vega MA, Corbí AL, Puig-Kröger A.; ''RUNX3 regulates the activity of the CD11a and CD49d integrin gene promoters.''; PubMed Europe PMC
  79. Jin YH, Jeon EJ, Li QL, Lee YH, Choi JK, Kim WJ, Lee KY, Bae SC.; ''Transforming growth factor-beta stimulates p300-dependent RUNX3 acetylation, which inhibits ubiquitination-mediated degradation.''; PubMed Europe PMC
  80. Song R, Koo BK, Yoon KJ, Yoon MJ, Yoo KW, Kim HT, Oh HJ, Kim YY, Han JK, Kim CH, Kong YY.; ''Neuralized-2 regulates a Notch ligand in cooperation with Mind bomb-1.''; PubMed Europe PMC
  81. Nakamura S, Senzaki K, Yoshikawa M, Nishimura M, Inoue K, Ito Y, Ozaki S, Shiga T.; ''Dynamic regulation of the expression of neurotrophin receptors by Runx3.''; PubMed Europe PMC
  82. Goh YM, Cinghu S, Hong ET, Lee YS, Kim JH, Jang JW, Li YH, Chi XZ, Lee KS, Wee H, Ito Y, Oh BC, Bae SC.; ''Src kinase phosphorylates RUNX3 at tyrosine residues and localizes the protein in the cytoplasm.''; PubMed Europe PMC
  83. Lee YS, Lee JW, Jang JW, Chi XZ, Kim JH, Li YH, Kim MK, Kim DM, Choi BS, Kim EG, Chung JH, Lee OJ, Lee YM, Suh JW, Chuang LS, Ito Y, Bae SC.; ''Runx3 inactivation is a crucial early event in the development of lung adenocarcinoma.''; PubMed Europe PMC
  84. Wildey GM, Patil S, Howe PH.; ''Smad3 potentiates transforming growth factor beta (TGFbeta )-induced apoptosis and expression of the BH3-only protein Bim in WEHI 231 B lymphocytes.''; PubMed Europe PMC
  85. Welcker M, Clurman BE.; ''FBW7 ubiquitin ligase: a tumour suppressor at the crossroads of cell division, growth and differentiation.''; PubMed Europe PMC
  86. McGill MA, Dho SE, Weinmaster G, McGlade CJ.; ''Numb regulates post-endocytic trafficking and degradation of Notch1.''; PubMed Europe PMC
  87. Bray SJ, Takada S, Harrison E, Shen SC, Ferguson-Smith AC.; ''The atypical mammalian ligand Delta-like homologue 1 (Dlk1) can regulate Notch signalling in Drosophila.''; PubMed Europe PMC
  88. Schroeter EH, Kisslinger JA, Kopan R.; ''Notch-1 signalling requires ligand-induced proteolytic release of intracellular domain.''; PubMed Europe PMC
  89. Luckey MA, Kimura MY, Waickman AT, Feigenbaum L, Singer A, Park JH.; ''The transcription factor ThPOK suppresses Runx3 and imposes CD4(+) lineage fate by inducing the SOCS suppressors of cytokine signaling.''; PubMed Europe PMC
  90. Zhou S, Fujimuro M, Hsieh JJ, Chen L, Miyamoto A, Weinmaster G, Hayward SD.; ''SKIP, a CBF1-associated protein, interacts with the ankyrin repeat domain of NotchIC To facilitate NotchIC function.''; PubMed Europe PMC
  91. Wilkins JA, Sansom OJ.; ''C-Myc is a critical mediator of the phenotypes of Apc loss in the intestine.''; PubMed Europe PMC
  92. Fryer CJ, Lamar E, Turbachova I, Kintner C, Jones KA.; ''Mastermind mediates chromatin-specific transcription and turnover of the Notch enhancer complex.''; PubMed Europe PMC
  93. Inoue K, Ozaki S, Shiga T, Ito K, Masuda T, Okado N, Iseda T, Kawaguchi S, Ogawa M, Bae SC, Yamashita N, Itohara S, Kudo N, Ito Y.; ''Runx3 controls the axonal projection of proprioceptive dorsal root ganglion neurons.''; PubMed Europe PMC
  94. Arnett KL, Hass M, McArthur DG, Ilagan MX, Aster JC, Kopan R, Blacklow SC.; ''Structural and mechanistic insights into cooperative assembly of dimeric Notch transcription complexes.''; PubMed Europe PMC
  95. Cairo S, Armengol C, Buendia MA.; ''Activation of Wnt and Myc signaling in hepatoblastoma.''; PubMed Europe PMC
  96. Lai EC, Deblandre GA, Kintner C, Rubin GM.; ''Drosophila neuralized is a ubiquitin ligase that promotes the internalization and degradation of delta.''; PubMed Europe PMC
  97. Wei SJ, Williams JG, Dang H, Darden TA, Betz BL, Humble MM, Chang FM, Trempus CS, Johnson K, Cannon RE, Tennant RW.; ''Identification of a specific motif of the DSS1 protein required for proteasome interaction and p53 protein degradation.''; PubMed Europe PMC
  98. Nishina S, Shiraha H, Nakanishi Y, Tanaka S, Matsubara M, Takaoka N, Uemura M, Horiguchi S, Kataoka J, Iwamuro M, Yagi T, Yamamoto K.; ''Restored expression of the tumor suppressor gene RUNX3 reduces cancer stem cells in hepatocellular carcinoma by suppressing Jagged1-Notch signaling.''; PubMed Europe PMC
  99. Mukherjee A, Veraksa A, Bauer A, Rosse C, Camonis J, Artavanis-Tsakonas S.; ''Regulation of Notch signalling by non-visual beta-arrestin.''; PubMed Europe PMC
  100. Baladrón V, Ruiz-Hidalgo MJ, Nueda ML, Díaz-Guerra MJ, García-Ramírez JJ, Bonvini E, Gubina E, Laborda J.; ''dlk acts as a negative regulator of Notch1 activation through interactions with specific EGF-like repeats.''; PubMed Europe PMC
  101. Landry JR, Kinston S, Knezevic K, de Bruijn MF, Wilson N, Nottingham WT, Peitz M, Edenhofer F, Pimanda JE, Ottersbach K, Göttgens B.; ''Runx genes are direct targets of Scl/Tal1 in the yolk sac and fetal liver.''; PubMed Europe PMC
  102. Oberg C, Li J, Pauley A, Wolf E, Gurney M, Lendahl U.; ''The Notch intracellular domain is ubiquitinated and negatively regulated by the mammalian Sel-10 homolog.''; PubMed Europe PMC
  103. Koo BK, Yoon KJ, Yoo KW, Lim HS, Song R, So JH, Kim CH, Kong YY.; ''Mind bomb-2 is an E3 ligase for Notch ligand.''; PubMed Europe PMC
  104. Yamamura Y, Lee WL, Inoue K, Ida H, Ito Y.; ''RUNX3 cooperates with FoxO3a to induce apoptosis in gastric cancer cells.''; PubMed Europe PMC
  105. Koo BK, Yoon MJ, Yoon KJ, Im SK, Kim YY, Kim CH, Suh PG, Jan YN, Kong YY.; ''An obligatory role of mind bomb-1 in notch signaling of mammalian development.''; PubMed Europe PMC
  106. Puig-Kröger A, Aguilera-Montilla N, Martínez-Nuñez R, Domínguez-Soto A, Sánchez-Cabo F, Martín-Gayo E, Zaballos A, Toribio ML, Groner Y, Ito Y, Dopazo A, Corcuera MT, Alonso Martín MJ, Vega MA, Corbí AL.; ''The novel RUNX3/p33 isoform is induced upon monocyte-derived dendritic cell maturation and downregulates IL-8 expression.''; PubMed Europe PMC
  107. Zhang H, Liu CY, Zha ZY, Zhao B, Yao J, Zhao S, Xiong Y, Lei QY, Guan KL.; ''TEAD transcription factors mediate the function of TAZ in cell growth and epithelial-mesenchymal transition.''; PubMed Europe PMC
  108. Gao J, Chen Y, Wu KC, Liu J, Zhao YQ, Pan YL, Du R, Zheng GR, Xiong YM, Xu HL, Fan DM.; ''RUNX3 directly interacts with intracellular domain of Notch1 and suppresses Notch signaling in hepatocellular carcinoma cells.''; PubMed Europe PMC
  109. Ebihara T, Ebihara T, Song C, Ryu SH, Plougastel-Douglas B, Yang L, Levanon D, Groner Y, Bern MD, Stappenbeck TS, Colonna M, Egawa T, Yokoyama WM.; ''Runx3 specifies lineage commitment of innate lymphoid cells.''; PubMed Europe PMC
  110. Reis BS, Rogoz A, Costa-Pinto FA, Taniuchi I, Mucida D.; ''Mutual expression of the transcription factors Runx3 and ThPOK regulates intestinal CD4⁺ T cell immunity.''; PubMed Europe PMC
  111. Park JI, Venteicher AS, Hong JY, Choi J, Jun S, Shkreli M, Chang W, Meng Z, Cheung P, Ji H, McLaughlin M, Veenstra TD, Nusse R, McCrea PD, Artandi SE.; ''Telomerase modulates Wnt signalling by association with target gene chromatin.''; PubMed Europe PMC
  112. Kishi N, Tang Z, Maeda Y, Hirai A, Mo R, Ito M, Suzuki S, Nakao K, Kinoshita T, Kadesch T, Hui C, Artavanis-Tsakonas S, Okano H, Matsuno K.; ''Murine homologs of deltex define a novel gene family involved in vertebrate Notch signaling and neurogenesis.''; PubMed Europe PMC
  113. Maier MM, Gessler M.; ''Comparative analysis of the human and mouse Hey1 promoter: Hey genes are new Notch target genes.''; PubMed Europe PMC
  114. Huppert SS, Le A, Schroeter EH, Mumm JS, Saxena MT, Milner LA, Kopan R.; ''Embryonic lethality in mice homozygous for a processing-deficient allele of Notch1.''; PubMed Europe PMC

History

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CompareRevisionActionTimeUserComment
101212view11:10, 1 November 2018ReactomeTeamreactome version 66
100750view20:35, 31 October 2018ReactomeTeamreactome version 65
100294view19:13, 31 October 2018ReactomeTeamreactome version 64
99840view15:56, 31 October 2018ReactomeTeamreactome version 63
99397view14:34, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
93569view11:27, 9 August 2017ReactomeTeamNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
26S proteasomeComplexR-HSA-177750 (Reactome)
ADPMetaboliteCHEBI:16761 (ChEBI)
ATPMetaboliteCHEBI:15422 (ChEBI)
Ac-CoAMetaboliteCHEBI:15351 (ChEBI)
Ac-K94,K171-RUNX3 ProteinQ13761 (Uniprot-TrEMBL)
Ac-K94,K171-RUNX3:CBFB:BRD2:CCND1:HDAC4ComplexR-HSA-8952063 (Reactome)
Ac-K94,K171-RUNX3:CBFB:BRD2:CCND1ComplexR-HSA-8952057 (Reactome)
Ac-K94,K171-RUNX3:CBFB:EP300:BRD2ComplexR-HSA-8951976 (Reactome)
Ac-K94,K171-RUNX3:CBFB:EP300ComplexR-HSA-8951959 (Reactome)
BCL2L11 gene ProteinENSG00000153094 (Ensembl)
BCL2L11 geneGeneProductENSG00000153094 (Ensembl)
BCL2L11ProteinO43521 (Uniprot-TrEMBL)
BRD2 ProteinP25440 (Uniprot-TrEMBL)
BRD2 homodimerComplexR-HSA-8951995 (Reactome)
CBFB ProteinQ13951 (Uniprot-TrEMBL)
CBFBProteinQ13951 (Uniprot-TrEMBL)
CCND1 ProteinP24385 (Uniprot-TrEMBL)
CCND1 gene ProteinENSG00000110092 (Ensembl)
CCND1 geneGeneProductENSG00000110092 (Ensembl)
CCND1ProteinP24385 (Uniprot-TrEMBL)
CDKN1A gene ProteinENSG00000124762 (Ensembl)
CDKN1A geneGeneProductENSG00000124762 (Ensembl)
CDKN1AProteinP38936 (Uniprot-TrEMBL)
CDKN2A gene ProteinENSG00000147889 (Ensembl)
CDKN2A geneGeneProductENSG00000147889 (Ensembl)
CH3COO-MetaboliteCHEBI:15366 (ChEBI)
CREBBP ProteinQ92793 (Uniprot-TrEMBL)
CTGF gene ProteinENSG00000118523 (Ensembl)
CTGF geneGeneProductENSG00000118523 (Ensembl)
CTGFProteinP29279 (Uniprot-TrEMBL)
CTNNB1 ProteinP35222 (Uniprot-TrEMBL)
CTNNB1:TCF7L2,(LEF1,TCF7L1,TCF7)ComplexR-HSA-8951429 (Reactome)
CTNNB1:TCF7L2,LEF1:CCND1 GeneComplexR-HSA-8853944 (Reactome)
CTNNB1:TCF7L2,LEF1ComplexR-HSA-8951439 (Reactome)
CoA-SHMetaboliteCHEBI:15346 (ChEBI)
Dimeric TGFB1ComplexR-HSA-170852 (Reactome)
EP300 ProteinQ09472 (Uniprot-TrEMBL)
EP300ProteinQ09472 (Uniprot-TrEMBL)
FOXO3 ProteinO43524 (Uniprot-TrEMBL)
FOXO3ProteinO43524 (Uniprot-TrEMBL)
GTP MetaboliteCHEBI:15996 (ChEBI)
H2OMetaboliteCHEBI:15377 (ChEBI)
HDAC4 ProteinP56524 (Uniprot-TrEMBL)
HDAC4ProteinP56524 (Uniprot-TrEMBL)
HES1 gene ProteinENSG00000114315 (Ensembl)
HES1 geneGeneProductENSG00000114315 (Ensembl)
HES1ProteinQ14469 (Uniprot-TrEMBL)
ITGA4 ProteinP13612 (Uniprot-TrEMBL)
ITGA4 gene ProteinENSG00000115232 (Ensembl)
ITGAL ProteinP20701 (Uniprot-TrEMBL)
ITGAL gene ProteinENSG00000005844 (Ensembl)
ITGAL gene,(ITGA4 gene)ComplexR-HSA-8949354 (Reactome)
ITGAL,(ITGA4)ComplexR-HSA-8949353 (Reactome)