Degradation of beta-catenin by the destruction complex (Homo sapiens)

From WikiPathways

Jump to: navigation, search
275, 10, 18, 35, 44...33, 39, 43, 52, 54...22235, 8, 10, 18, 19, 35...9, 36, 5326, 372217, 25, 35, 564021, 30, 47, 498, 10, 18, 19, 35...4, 7, 11-13, 29...4028, 537, 16, 45338207, 31, 33, 54, 5514226, 15, 24, 34, 35, 41cytosolnucleoplasmPPP2R1B CSNK1A1 K63polyUbp-T41,S45CTNNB1:p-AXIN:GSK3:CK1alpha:ub-APC:PP2A:AMER1 complexPPP2R5E TLE2 PPP2R1A PSMA4 LEF1 TLE1 TCF7L1 PSMD6 PPP2R1A PPP2R1A CSNK1A1 ubiquitinatedphospho-beta-catenin:RBX1:SCF(beta-TrCP1) complexPPP2CB PSME4 GSK3B SKP1 PSMD7 PSME2 p-ub-APC PPP2R5A 'canonical' WNTtargetgenes:TCF/LEFMYC gene PPP2R1B PPP2R5D PSMB10 TCF7L1 p-S33,S37,T41,S45-beta-catenin:p-AXIN:GSK3:CK1alpha:ub-APC:PP2A:AMER1 complexPPP2R5B GSK3B CUL1 p-S33,S37,T41,S45CTNNB1:p-AXIN:CK1alpha:GSK3B:phospho-ub-APC (20 aa repeat region):PP2A:AMER1 complexPPP2R1B PSMD5 PPP2CB p-T519,S524,S531-AXIN1 CSNK1A1 PPP2CB PSMC1 TCF7 K63polyUb-APC TLE3 TCF7L1 PPP2R5C RBX1 TCF/LEFPPP2CA TLE2 CTBP1 TLE4 PPP2CA PPP2R5A CSNK1A1 CTNNB1 RPS27A(1-76) AMER1PPP2CB K63polyUb-APC TLE:AESPSMD1 PPP2CA AXIN2 mRNA TCF7L1 UBC(153-228) AMER1 PPP2R1B PSMB3 PPP2R5D unknown ubiquitinligaseCTBPsPPP2R5C PPP2CB PPP2R1A PPP2R5E PPP2R5E ATPBTRC K63polyUb-APCPSMB7 PPP2R5D PPP2R1B K63polyUb-APC p-T519,S524,S531-AXIN1 GSK3B PPP2R5D p-T519,S524,S531-AXIN1 PSMB9 PPP2R5E MYC gene PPP2R5A GSK3B AMER1 PPP2R5E CTBP2 PSMD11 CUL1 SKP1 ATPTLE3 TLE4 p-S33,S37,T41,S45 CTNNB1 BTRC ZRANB1:K63polyUb-APCPPP2R5E PPP2R5D UBC(153-228) PPP2R5B CSNK1A1 PPP2R5C p-T519,S524,S531-AXIN1 PPP2R5B UBC(609-684) TLE1 PPP2CA PSME1 PPP2R5B TLE2 UBB(77-152) ATPPPP2R5D PPP2R1A GSK3Bp-T519,S524,S531-AXIN1 PSMD12 ZRANB1AES K63polyUb-APC PPP2CA p-S33,S37,T41,S45 CTNNB1 GSK3B PPP2R5B PPP2R1A AMER1 p-T41,S45 CTNNB1 PPP2R1A RBX1:SKP1:CUL1:beta-TrCP1:phosphorylated beta-catenin complexPSMB1 CSNK1A1 p-T519,S524,S531-AXIN1 CSNK1A1UBC(457-532) PPP2CA PPP2R1A PPP2R5A UBC(1-76) TCF7L1 LEF1 GSK3B HDAC1TLE3 p-ub-APC CTBP2 PSMD2 GSK3B GSK3B APCUBC(229-304) CTNNB1:p-AXIN:GSK3:CK1alpha:ub-APC:PP2A:AMER1 complexp-T519,S524,S531-AXIN1 PPP2CB PPP2R5C PPP2R5A 'canonical' WNTtargetgenes:TCF/LEF:TLEtetramer:HDAC1PPP2R5A PPP2R5A TCF7 PPP2R5C 'canonical' WNTtarget genesCSNK1A1 UBC(77-152) AXIN2 gene AMER1 geneUbAMER1 PPP2CB UBC(305-380) PSMC5 PPP2CA ADPFRAT2 TCF7L1 AMER1 AXIN:GSK3:CK1alpha:ub-APC:PP2A:AMER1 complexTCF7L2 PPP2CA ATPADPp-ub-APC PSMD9 TCF7 AXIN2 gene PPP2R5A SKP1 UBA52(1-76) UBB(153-228) AMER1 PPP2R5B K63polyUb-APC TCF7L2/TCF7L1:CTBPsTLERBX1 PSMA6 p-S33,S37,T41,S45 CTNNB1 TLE2 PSMF1 PPP2R5E AMER1 PPP2R5D PPP2R5B CTBP1 CSNK1A1 UBC(381-456) UBB(77-152) ADPUBC(457-532) GSK3B PPP2R5B PPP2R1A PPP2R5D PPP2R5C AXIN2 gene PPP2R5B p-S33,S37,T41,S45 CTNNB1 TCF7L2 TLE1 p-S33,S37,T41,S45CTNNB1:p-AXIN:CK1alpha:GSK3B:phospho-ub-APC (20 aa repeat region):PP2A:AMER1 complexPSMC4 UBC(229-304) PPP2R5A BTRC:CUL1:RBX1:SKP1PPP2R5B PPP2R1B HDAC1 PSMB2 PSMC6 UBB(1-76) CTNNB1PPP2R1B 'canonical' WNTtarget genetranscriptsUBC(305-380) PPP2R1B FRAT1,2:GSK3betaPPP2R5A PPP2R5C TLE3 ATPMYC mRNA PSMA7 PSMD4 PSMB4 TCF7 PPP2R1A ADPUBC(533-608) PSMD13 p-S37,T41,S45CTNNB1:p-AXIN:GSK3:CK1alpha:ub-APC:PP2A:AMER1 complexAESTLE tetramerPPP2R5D UBC(1-76) PSMA1 RPS27A(1-76) TLE1 CUL1 PPP2R1B PPP2CA TLE4 MYC gene AXIN1PPP2R5B p-S45CTNNB1:p-Axin:GSK3:CK1alpha:ub-APC:PP2A:AMER1 complexp-AXIN:CK1alpha:GSK3B:phospho-APC (20 aa repeat region):PP2A:AMER1 complexLEF1 PP2ATCF7L2/TCF7L1PPP2R1A K63polyUb-APC CSNK1A1 PPP2R5C GSK3B PPP2R5C TLE4 PPP2R5D PSMB6 LEF1 PPP2CA PPP2R1B PPP2R5E PSME3 PSMA8 UBC(381-456) TLE2 PPP2R1A PPP2R5C PPP2R5A BTRC PPP2CB PPP2R1B UBC(609-684) TCF7L2 p-S37,T41,S45, CTNNB1 ATPK63polyUb-APC CSNK1A1 PPP2R5E p-ub-APC TLE1 PSMD3 PPP2R5D PPP2R5E PSMB8 AXIN2 gene PPP2R5A PPP2R1B GSK3B PPP2CA p-S33,S37,T41,S45 CTNNB1 PSMC2 AMER1 p-T519,S524,S531-AXIN1 'canonical' WNTtargetgene:TCF/LEF:TLEtetramerPPP2CB AMER1 TCF7L2 PSMD8 p-AXIN:GSK3:CK1alpha:ub-APC:PP2A:AMER1 complexPSMD14 ADPTCF7L2 PPP2R5D PPP2CA PPP2R5B PSMB11 FRAT1 CSNK1A1 PPP2R5E p-T519,S524,S531-AXIN1 UBC(77-152) 26S proteasomePPP2CB PPP2R5C PPP2CB PSMB5 RBX1 PPP2R5C PSMC3 p-T519,S524,S531-AXIN1 PPP2CB ZRANB1 AMER1 p-S45 CTNNB1 PPP2R5C K63polyUb-APC ADPPPP2R1A AXIN1 geneUBA52(1-76) UBB(153-228) PPP2CA UBC(533-608) PSMD10 MYC gene PPP2R5D TLE3 PPP2CB PPP2R5E TLE4 PPP2R5E SHFM1 PSMA3 GSK3B PSMA2 PPP2R5B AMER1 AMER1 UBB(1-76) p-ub-APC PSMA5 CSNK1A1 PPP2R1B GSK3B AXIN1 p-T519,S524,S531-AXIN1 TCF7L2 PPP2R5A 1, 4222, 32


Description

The beta-catenin destruction complex plays a key role in the canonical Wnt signaling pathway. In the absence of Wnt signaling, this complex controls the levels of cytoplamic beta-catenin. Beta-catenin associates with and is phosphorylated by the destruction complex. Phosphorylated beta-catenin is recognized and ubiquitinated by the SCF-beta TrCP ubiquitin ligase complex and is subsequently degraded by the proteasome (reviewed in Kimelman and Xu, 2006). View original pathway at Reactome.

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 195253
Reactome-version 
Reactome version: 75
Reactome Author 
Reactome Author: Kimelman, D

Quality Tags

Ontology Terms

 

Bibliography

View all...
  1. Freemantle SJ, Portland HB, Ewings K, Dmitrovsky F, DiPetrillo K, Spinella MJ, Dmitrovsky E.; ''Characterization and tissue-specific expression of human GSK-3-binding proteins FRAT1 and FRAT2.''; PubMed Europe PMC Scholia
  2. 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 Scholia
  3. Tran H, Hamada F, Schwarz-Romond T, Bienz M.; ''Trabid, a new positive regulator of Wnt-induced transcription with preference for binding and cleaving K63-linked ubiquitin chains.''; PubMed Europe PMC Scholia
  4. Willert K, Shibamoto S, Nusse R.; ''Wnt-induced dephosphorylation of axin releases beta-catenin from the axin complex.''; PubMed Europe PMC Scholia
  5. Brantjes H, Barker N, van Es J, Clevers H.; ''TCF: Lady Justice casting the final verdict on the outcome of Wnt signalling.''; PubMed Europe PMC Scholia
  6. Muhr J, Andersson E, Persson M, Jessell TM, Ericson J.; ''Groucho-mediated transcriptional repression establishes progenitor cell pattern and neuronal fate in the ventral neural tube.''; PubMed Europe PMC Scholia
  7. Saito-Diaz K, Chen TW, Wang X, Thorne CA, Wallace HA, Page-McCaw A, Lee E.; ''The way Wnt works: components and mechanism.''; PubMed Europe PMC Scholia
  8. Chen G, Nguyen PH, Courey AJ.; ''A role for Groucho tetramerization in transcriptional repression.''; PubMed Europe PMC Scholia
  9. Dajani R, Fraser E, Roe SM, Yeo M, Good VM, Thompson V, Dale TC, Pearl LH.; ''Structural basis for recruitment of glycogen synthase kinase 3beta to the axin-APC scaffold complex.''; PubMed Europe PMC Scholia
  10. Levanon D, Goldstein RE, Bernstein Y, Tang H, Goldenberg D, Stifani S, Paroush Z, Groner Y.; ''Transcriptional repression by AML1 and LEF-1 is mediated by the TLE/Groucho corepressors.''; PubMed Europe PMC Scholia
  11. Ikeda S, Kishida S, Yamamoto H, Murai H, Koyama S, Kikuchi A.; ''Axin, a negative regulator of the Wnt signaling pathway, forms a complex with GSK-3beta and beta-catenin and promotes GSK-3beta-dependent phosphorylation of beta-catenin.''; PubMed Europe PMC Scholia
  12. Luo W, Peterson A, Garcia BA, Coombs G, Kofahl B, Heinrich R, Shabanowitz J, Hunt DF, Yost HJ, Virshup DM.; ''Protein phosphatase 1 regulates assembly and function of the beta-catenin degradation complex.''; PubMed Europe PMC Scholia
  13. Jho E, Lomvardas S, Costantini F.; ''A GSK3beta phosphorylation site in axin modulates interaction with beta-catenin and Tcf-mediated gene expression.''; PubMed Europe PMC Scholia
  14. Amit S, Hatzubai A, Birman Y, Andersen JS, Ben-Shushan E, Mann M, Ben-Neriah Y, Alkalay I.; ''Axin-mediated CKI phosphorylation of beta-catenin at Ser 45: a molecular switch for the Wnt pathway.''; PubMed Europe PMC Scholia
  15. Miyasaka H, Choudhury BK, Hou EW, Li SS.; ''Molecular cloning and expression of mouse and human cDNA encoding AES and ESG proteins with strong similarity to Drosophila enhancer of split groucho protein.''; PubMed Europe PMC Scholia
  16. Salahshor S, Woodgett JR.; ''The links between axin and carcinogenesis.''; PubMed Europe PMC Scholia
  17. Choi CY, Kim YH, Kwon HJ, Kim Y.; ''The homeodomain protein NK-3 recruits Groucho and a histone deacetylase complex to repress transcription.''; PubMed Europe PMC Scholia
  18. Arce L, Pate KT, Waterman ML.; ''Groucho binds two conserved regions of LEF-1 for HDAC-dependent repression.''; PubMed Europe PMC Scholia
  19. Song H, Hasson P, Paroush Z, Courey AJ.; ''Groucho oligomerization is required for repression in vivo.''; PubMed Europe PMC Scholia
  20. Wu G, Xu G, Schulman BA, Jeffrey PD, Harper JW, Pavletich NP.; ''Structure of a beta-TrCP1-Skp1-beta-catenin complex: destruction motif binding and lysine specificity of the SCF(beta-TrCP1) ubiquitin ligase.''; PubMed Europe PMC Scholia
  21. Tran H, Polakis P.; ''Reversible modification of adenomatous polyposis coli (APC) with K63-linked polyubiquitin regulates the assembly and activity of the β-catenin destruction complex.''; PubMed Europe PMC Scholia
  22. Liu C, Li Y, Semenov M, Han C, Baeg GH, Tan Y, Zhang Z, Lin X, He X.; ''Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism.''; PubMed Europe PMC Scholia
  23. Liu J, Xing Y, Hinds TR, Zheng J, Xu W.; ''The third 20 amino acid repeat is the tightest binding site of APC for beta-catenin.''; PubMed Europe PMC Scholia
  24. Roose J, Molenaar M, Peterson J, Hurenkamp J, Brantjes H, Moerer P, van de Wetering M, Destrée O, Clevers H.; ''The Xenopus Wnt effector XTcf-3 interacts with Groucho-related transcriptional repressors.''; PubMed Europe PMC Scholia
  25. Winkler CJ, Ponce A, Courey AJ.; ''Groucho-mediated repression may result from a histone deacetylase-dependent increase in nucleosome density.''; PubMed Europe PMC Scholia
  26. Latres E, Chiaur DS, Pagano M.; ''The human F box protein beta-Trcp associates with the Cul1/Skp1 complex and regulates the stability of beta-catenin.''; PubMed Europe PMC Scholia
  27. Kimelman D, Xu W.; ''beta-catenin destruction complex: insights and questions from a structural perspective.''; PubMed Europe PMC Scholia
  28. Rivera MN, Kim WJ, Wells J, Driscoll DR, Brannigan BW, Han M, Kim JC, Feinberg AP, Gerald WL, Vargas SO, Chin L, Iafrate AJ, Bell DW, Haber DA.; ''An X chromosome gene, WTX, is commonly inactivated in Wilms tumor.''; PubMed Europe PMC Scholia
  29. Kim SE, Huang H, Zhao M, Zhang X, Zhang A, Semonov MV, MacDonald BT, Zhang X, Garcia Abreu J, Peng L, He X.; ''Wnt stabilization of β-catenin reveals principles for morphogen receptor-scaffold assemblies.''; PubMed Europe PMC Scholia
  30. Su Y, Fu C, Ishikawa S, Stella A, Kojima M, Shitoh K, Schreiber EM, Day BW, Liu B.; ''APC is essential for targeting phosphorylated beta-catenin to the SCFbeta-TrCP ubiquitin ligase.''; PubMed Europe PMC Scholia
  31. Cinnamon E, Paroush Z.; ''Context-dependent regulation of Groucho/TLE-mediated repression.''; PubMed Europe PMC Scholia
  32. Voges D, Zwickl P, Baumeister W.; ''The 26S proteasome: a molecular machine designed for controlled proteolysis.''; PubMed Europe PMC Scholia
  33. Tang W, Dodge M, Gundapaneni D, Michnoff C, Roth M, Lum L.; ''A genome-wide RNAi screen for Wnt/beta-catenin pathway components identifies unexpected roles for TCF transcription factors in cancer.''; PubMed Europe PMC Scholia
  34. Swingler TE, Bess KL, Yao J, Stifani S, Jayaraman PS.; ''The proline-rich homeodomain protein recruits members of the Groucho/Transducin-like enhancer of split protein family to co-repress transcription in hematopoietic cells.''; PubMed Europe PMC Scholia
  35. Brantjes H, Roose J, van De Wetering M, Clevers H.; ''All Tcf HMG box transcription factors interact with Groucho-related co-repressors.''; PubMed Europe PMC Scholia
  36. Seeling JM, Miller JR, Gil R, Moon RT, White R, Virshup DM.; ''Regulation of beta-catenin signaling by the B56 subunit of protein phosphatase 2A.''; PubMed Europe PMC Scholia
  37. Winston JT, Strack P, Beer-Romero P, Chu CY, Elledge SJ, Harper JW.; ''The SCFbeta-TRCP-ubiquitin ligase complex associates specifically with phosphorylated destruction motifs in IkappaBalpha and beta-catenin and stimulates IkappaBalpha ubiquitination in vitro.''; PubMed Europe PMC Scholia
  38. Calviello G, Resci F, Serini S, Piccioni E, Toesca A, Boninsegna A, Monego G, Ranelletti FO, Palozza P.; ''Docosahexaenoic acid induces proteasome-dependent degradation of beta-catenin, down-regulation of survivin and apoptosis in human colorectal cancer cells not expressing COX-2.''; PubMed Europe PMC Scholia
  39. Hamada F, Bienz M.; ''The APC tumor suppressor binds to C-terminal binding protein to divert nuclear beta-catenin from TCF.''; PubMed Europe PMC Scholia
  40. Xing Y, Clements WK, Le Trong I, Hinds TR, Stenkamp R, Kimelman D, Xu W.; ''Crystal structure of a beta-catenin/APC complex reveals a critical role for APC phosphorylation in APC function.''; PubMed Europe PMC Scholia
  41. Ren B, Chee KJ, Kim TH, Maniatis T.; ''PRDI-BF1/Blimp-1 repression is mediated by corepressors of the Groucho family of proteins.''; PubMed Europe PMC Scholia
  42. Saitoh T, Moriwaki J, Koike J, Takagi A, Miwa T, Shiokawa K, Katoh M.; ''Molecular cloning and characterization of FRAT2, encoding a positive regulator of the WNT signaling pathway.''; PubMed Europe PMC Scholia
  43. Brannon M, Brown JD, Bates R, Kimelman D, Moon RT.; ''XCtBP is a XTcf-3 co-repressor with roles throughout Xenopus development.''; PubMed Europe PMC Scholia
  44. Daniels DL, Weis WI.; ''Beta-catenin directly displaces Groucho/TLE repressors from Tcf/Lef in Wnt-mediated transcription activation.''; PubMed Europe PMC Scholia
  45. Zeng L, Fagotto F, Zhang T, Hsu W, Vasicek TJ, Perry WL, Lee JJ, Tilghman SM, Gumbiner BM, Costantini F.; ''The mouse Fused locus encodes Axin, an inhibitor of the Wnt signaling pathway that regulates embryonic axis formation.''; PubMed Europe PMC Scholia
  46. Hanaki H, Yamamoto H, Sakane H, Matsumoto S, Ohdan H, Sato A, Kikuchi A.; ''An anti-Wnt5a antibody suppresses metastasis of gastric cancer cells in vivo by inhibiting receptor-mediated endocytosis.''; PubMed Europe PMC Scholia
  47. Tauriello DV, Haegebarth A, Kuper I, Edelmann MJ, Henraat M, Canninga-van Dijk MR, Kessler BM, Clevers H, Maurice MM.; ''Loss of the tumor suppressor CYLD enhances Wnt/beta-catenin signaling through K63-linked ubiquitination of Dvl.''; PubMed Europe PMC Scholia
  48. Yamamoto H, Kishida S, Kishida M, Ikeda S, Takada S, Kikuchi A.; ''Phosphorylation of axin, a Wnt signal negative regulator, by glycogen synthase kinase-3beta regulates its stability.''; PubMed Europe PMC Scholia
  49. Kim MJ, Chia IV, Costantini F.; ''SUMOylation target sites at the C terminus protect Axin from ubiquitination and confer protein stability.''; PubMed Europe PMC Scholia
  50. Chen G, Courey AJ.; ''Groucho/TLE family proteins and transcriptional repression.''; PubMed Europe PMC Scholia
  51. Pinto M, Lobe CG.; ''Products of the grg (Groucho-related gene) family can dimerize through the amino-terminal Q domain.''; PubMed Europe PMC Scholia
  52. Valenta T, Lukas J, Korinek V.; ''HMG box transcription factor TCF-4's interaction with CtBP1 controls the expression of the Wnt target Axin2/Conductin in human embryonic kidney cells.''; PubMed Europe PMC Scholia
  53. Major MB, Camp ND, Berndt JD, Yi X, Goldenberg SJ, Hubbert C, Biechele TL, Gingras AC, Zheng N, Maccoss MJ, Angers S, Moon RT.; ''Wilms tumor suppressor WTX negatively regulates WNT/beta-catenin signaling.''; PubMed Europe PMC Scholia
  54. Duval A, Rolland S, Tubacher E, Bui H, Thomas G, Hamelin R.; ''The human T-cell transcription factor-4 gene: structure, extensive characterization of alternative splicings, and mutational analysis in colorectal cancer cell lines.''; PubMed Europe PMC Scholia
  55. Cuilliere-Dartigues P, El-Bchiri J, Krimi A, Buhard O, Fontanges P, Fléjou JF, Hamelin R, Duval A.; ''TCF-4 isoforms absent in TCF-4 mutated MSI-H colorectal cancer cells colocalize with nuclear CtBP and repress TCF-4-mediated transcription.''; PubMed Europe PMC Scholia
  56. Chen G, Fernandez J, Mische S, Courey AJ.; ''A functional interaction between the histone deacetylase Rpd3 and the corepressor groucho in Drosophila development.''; PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
114976view16:50, 25 January 2021ReactomeTeamReactome version 75
113420view11:49, 2 November 2020ReactomeTeamReactome version 74
112622view16:00, 9 October 2020ReactomeTeamReactome version 73
101538view11:40, 1 November 2018ReactomeTeamreactome version 66
101073view21:22, 31 October 2018ReactomeTeamreactome version 65
100603view19:57, 31 October 2018ReactomeTeamreactome version 64
100154view16:42, 31 October 2018ReactomeTeamreactome version 63
99704view15:10, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
93998view13:50, 16 August 2017ReactomeTeamreactome version 61
93607view11:28, 9 August 2017ReactomeTeamreactome version 61
87171view19:24, 18 July 2016MkutmonOntology Term : 'Wnt signaling pathway' added !
86716view09:24, 11 July 2016ReactomeTeamreactome version 56
83396view11:07, 18 November 2015ReactomeTeamVersion54
81590view13:07, 21 August 2015ReactomeTeamVersion53
77050view08:35, 17 July 2014ReactomeTeamFixed remaining interactions
76755view12:11, 16 July 2014ReactomeTeamFixed remaining interactions
76080view10:14, 11 June 2014ReactomeTeamRe-fixing comment source
75790view11:32, 10 June 2014ReactomeTeamReactome 48 Update
75140view14:08, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74831view10:05, 30 April 2014ReactomeTeamReactome46
74787view08:52, 30 April 2014ReactomeTeamNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
'canonical' WNT

target gene:TCF/LEF:TLE

tetramer
ComplexR-HSA-8944351 (Reactome)
'canonical' WNT

target genes:TCF/LEF:TLE

tetramer:HDAC1
ComplexR-HSA-8944365 (Reactome)
'canonical' WNT

target

genes:TCF/LEF
ComplexR-HSA-8944354 (Reactome)
'canonical' WNT

target gene

transcripts
ComplexR-HSA-4411358 (Reactome)
'canonical' WNT target genesComplexR-HSA-4411390 (Reactome)
26S proteasomeComplexR-HSA-68819 (Reactome)
ADPMetaboliteCHEBI:456216 (ChEBI)
AES ProteinQ08117 (Uniprot-TrEMBL)
AESProteinQ08117 (Uniprot-TrEMBL)
AMER1 ProteinQ5JTC6 (Uniprot-TrEMBL)
AMER1 geneGeneProductENSG00000184675 (Ensembl)
AMER1ProteinQ5JTC6 (Uniprot-TrEMBL)
APCProteinP25054 (Uniprot-TrEMBL)
ATPMetaboliteCHEBI:30616 (ChEBI)
AXIN1 ProteinO15169 (Uniprot-TrEMBL)
AXIN1 geneGeneProductENSG00000103126 (Ensembl)
AXIN1ProteinO15169 (Uniprot-TrEMBL)
AXIN2 gene ProteinENSG00000168646 (Ensembl)
AXIN2 mRNA ProteinENST00000307078 (Ensembl)
AXIN:GSK3:CK1alpha:ub-APC:PP2A:AMER1 complexComplexR-HSA-195250 (Reactome)
BTRC ProteinQ9Y297 (Uniprot-TrEMBL)
BTRC:CUL1:RBX1:SKP1ComplexR-HSA-206748 (Reactome)
CSNK1A1 ProteinP48729 (Uniprot-TrEMBL)
CSNK1A1ProteinP48729 (Uniprot-TrEMBL)
CTBP1 ProteinQ13363 (Uniprot-TrEMBL)
CTBP2 ProteinP56545 (Uniprot-TrEMBL)
CTBPsComplexR-HSA-5333992 (Reactome)
CTNNB1 ProteinP35222 (Uniprot-TrEMBL)
CTNNB1:p-AXIN:GSK3:CK1alpha:ub-APC:PP2A:AMER1 complexComplexR-HSA-3601581 (Reactome)
CTNNB1ProteinP35222 (Uniprot-TrEMBL)
CUL1 ProteinQ13616 (Uniprot-TrEMBL)
FRAT1 ProteinQ92837 (Uniprot-TrEMBL)
FRAT1,2:GSK3betaComplexR-HSA-1226052 (Reactome)
FRAT2 ProteinO75474 (Uniprot-TrEMBL)
GSK3B ProteinP49841 (Uniprot-TrEMBL)
GSK3BProteinP49841 (Uniprot-TrEMBL)
HDAC1 ProteinQ13547 (Uniprot-TrEMBL)
HDAC1ProteinQ13547 (Uniprot-TrEMBL)
K63polyUb-APC ProteinP25054 (Uniprot-TrEMBL)
K63polyUb-APCProteinP25054 (Uniprot-TrEMBL)
K63polyUbR-HSA-450152 (Reactome)
LEF1 ProteinQ9UJU2 (Uniprot-TrEMBL)
MYC gene ProteinENSG00000136997 (Ensembl)
MYC mRNA ProteinENST00000377970 (Ensembl)
PP2AComplexR-HSA-196206 (Reactome)
PPP2CA ProteinP67775 (Uniprot-TrEMBL)
PPP2CB ProteinP62714 (Uniprot-TrEMBL)
PPP2R1A ProteinP30153 (Uniprot-TrEMBL)
PPP2R1B ProteinP30154 (Uniprot-TrEMBL)
PPP2R5A ProteinQ15172 (Uniprot-TrEMBL)
PPP2R5B ProteinQ15173 (Uniprot-TrEMBL)
PPP2R5C ProteinQ13362 (Uniprot-TrEMBL)
PPP2R5D ProteinQ14738 (Uniprot-TrEMBL)
PPP2R5E ProteinQ16537 (Uniprot-TrEMBL)
PSMA1 ProteinP25786 (Uniprot-TrEMBL)
PSMA2 ProteinP25787 (Uniprot-TrEMBL)
PSMA3 ProteinP25788 (Uniprot-TrEMBL)
PSMA4 ProteinP25789 (Uniprot-TrEMBL)
PSMA5 ProteinP28066 (Uniprot-TrEMBL)
PSMA6 ProteinP60900 (Uniprot-TrEMBL)
PSMA7 ProteinO14818 (Uniprot-TrEMBL)
PSMA8 ProteinQ8TAA3 (Uniprot-TrEMBL)
PSMB1 ProteinP20618 (Uniprot-TrEMBL)
PSMB10 ProteinP40306 (Uniprot-TrEMBL)
PSMB11 ProteinA5LHX3 (Uniprot-TrEMBL)
PSMB2 ProteinP49721 (Uniprot-TrEMBL)
PSMB3 ProteinP49720 (Uniprot-TrEMBL)
PSMB4 ProteinP28070 (Uniprot-TrEMBL)
PSMB5 ProteinP28074 (Uniprot-TrEMBL)
PSMB6 ProteinP28072 (Uniprot-TrEMBL)
PSMB7 ProteinQ99436 (Uniprot-TrEMBL)
PSMB8 ProteinP28062 (Uniprot-TrEMBL)
PSMB9 ProteinP28065 (Uniprot-TrEMBL)
PSMC1 ProteinP62191 (Uniprot-TrEMBL)
PSMC2 ProteinP35998 (Uniprot-TrEMBL)
PSMC3 ProteinP17980 (Uniprot-TrEMBL)
PSMC4 ProteinP43686 (Uniprot-TrEMBL)
PSMC5 ProteinP62195 (Uniprot-TrEMBL)
PSMC6 ProteinP62333 (Uniprot-TrEMBL)
PSMD1 ProteinQ99460 (Uniprot-TrEMBL)
PSMD10 ProteinO75832 (Uniprot-TrEMBL)
PSMD11 ProteinO00231 (Uniprot-TrEMBL)
PSMD12 ProteinO00232 (Uniprot-TrEMBL)
PSMD13 ProteinQ9UNM6 (Uniprot-TrEMBL)
PSMD14 ProteinO00487 (Uniprot-TrEMBL)
PSMD2 ProteinQ13200 (Uniprot-TrEMBL)
PSMD3 ProteinO43242 (Uniprot-TrEMBL)
PSMD4 ProteinP55036 (Uniprot-TrEMBL)
PSMD5 ProteinQ16401 (Uniprot-TrEMBL)
PSMD6 ProteinQ15008 (Uniprot-TrEMBL)
PSMD7 ProteinP51665 (Uniprot-TrEMBL)
PSMD8 ProteinP48556 (Uniprot-TrEMBL)
PSMD9 ProteinO00233 (Uniprot-TrEMBL)
PSME1 ProteinQ06323 (Uniprot-TrEMBL)
PSME2 ProteinQ9UL46 (Uniprot-TrEMBL)
PSME3 ProteinP61289 (Uniprot-TrEMBL)
PSME4 ProteinQ14997 (Uniprot-TrEMBL)
PSMF1 ProteinQ92530 (Uniprot-TrEMBL)
RBX1 ProteinP62877 (Uniprot-TrEMBL)
RBX1:SKP1:CUL1:beta-TrCP1:phosphorylated beta-catenin complexComplexR-HSA-2130280 (Reactome) B-TrCP associates with phosphorylated beta-catenin through the B-TrCP WD40 repeat region. Currently, it is unclear whether the ubiquitin ligase binds beta-catenin after it leaves the complex. It is equally possible that it binds beta-catenin while beta-catenin is still bound to Axin.
RPS27A(1-76) ProteinP62979 (Uniprot-TrEMBL)
SHFM1 ProteinP60896 (Uniprot-TrEMBL)
SKP1 ProteinP63208 (Uniprot-TrEMBL)
TCF/LEFComplexR-HSA-3299546 (Reactome)
TCF7 ProteinP36402 (Uniprot-TrEMBL)
TCF7L1 ProteinQ9HCS4 (Uniprot-TrEMBL)
TCF7L2 ProteinQ9NQB0 (Uniprot-TrEMBL)
TCF7L2/TCF7L1:CTBPsComplexR-HSA-5334048 (Reactome)
TCF7L2/TCF7L1ComplexR-HSA-5334046 (Reactome)
TLE tetramerComplexR-HSA-3299565 (Reactome)
TLE1 ProteinQ04724 (Uniprot-TrEMBL)
TLE2 ProteinQ04725 (Uniprot-TrEMBL)
TLE3 ProteinQ04726 (Uniprot-TrEMBL)
TLE4 ProteinQ04727 (Uniprot-TrEMBL)
TLE:AESComplexR-HSA-4649013 (Reactome)
TLEComplexR-HSA-4649011 (Reactome)
UBA52(1-76) ProteinP62987 (Uniprot-TrEMBL)
UBB(1-76) ProteinP0CG47 (Uniprot-TrEMBL)
UBB(153-228) ProteinP0CG47 (Uniprot-TrEMBL)
UBB(77-152) ProteinP0CG47 (Uniprot-TrEMBL)
UBC(1-76) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(153-228) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(229-304) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(305-380) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(381-456) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(457-532) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(533-608) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(609-684) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(77-152) ProteinP0CG48 (Uniprot-TrEMBL)
UbComplexR-HSA-113595 (Reactome)
ZRANB1 ProteinQ9UGI0 (Uniprot-TrEMBL)
ZRANB1:K63polyUb-APCComplexR-HSA-6781912 (Reactome)
ZRANB1ProteinQ9UGI0 (Uniprot-TrEMBL)
p-AXIN:CK1alpha:GSK3B:phospho-APC (20 aa repeat region):PP2A:AMER1 complexComplexR-HSA-196222 (Reactome) In this complex Axin is bound to beta-catenin.
p-AXIN:GSK3:CK1alpha:ub-APC:PP2A:AMER1 complexComplexR-HSA-3601577 (Reactome)
p-S33,S37,T41,S45 CTNNB1:p-AXIN:CK1alpha:GSK3B:phospho-ub-APC (20 aa repeat region):PP2A:AMER1 complexComplexR-HSA-195297 (Reactome) In this complex Axin is bound to beta-catenin.
p-S33,S37,T41,S45 CTNNB1:p-AXIN:CK1alpha:GSK3B:phospho-ub-APC (20 aa repeat region):PP2A:AMER1 complexComplexR-HSA-195322 (Reactome) In this form of the destruction complex, beta-catenin is no longer associated with Axin, but instead with phospho-(20aa) APC.
p-S33,S37,T41,S45 CTNNB1 ProteinP35222 (Uniprot-TrEMBL)
p-S33,S37,T41,S45-beta-catenin:p-AXIN:GSK3:CK1alpha:ub-APC:PP2A:AMER1 complexComplexR-HSA-195282 (Reactome)
p-S37,T41,S45 CTNNB1:p-AXIN:GSK3:CK1alpha:ub-APC:PP2A:AMER1 complexComplexR-HSA-195305 (Reactome)
p-S37,T41,S45, CTNNB1 ProteinP35222 (Uniprot-TrEMBL)
p-S45 CTNNB1:p-Axin:GSK3:CK1alpha:ub-APC:PP2A:AMER1 complexComplexR-HSA-195277 (Reactome)
p-S45 CTNNB1 ProteinP35222 (Uniprot-TrEMBL)
p-T41,S45 CTNNB1:p-AXIN:GSK3:CK1alpha:ub-APC:PP2A:AMER1 complexComplexR-HSA-195313 (Reactome)
p-T41,S45 CTNNB1 ProteinP35222 (Uniprot-TrEMBL)
p-T519,S524,S531-AXIN1 ProteinO15169 (Uniprot-TrEMBL)
p-ub-APC ProteinP25054 (Uniprot-TrEMBL)
ubiquitinated phospho-beta-catenin:RBX1:SCF(beta-TrCP1) complexComplexR-HSA-2130284 (Reactome)
unknown ubiquitin ligaseR-HSA-5250898 (Reactome)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
'canonical' WNT

target gene:TCF/LEF:TLE

tetramer
ArrowR-HSA-8944349 (Reactome)
'canonical' WNT

target gene:TCF/LEF:TLE

tetramer
R-HSA-4641231 (Reactome)
'canonical' WNT

target genes:TCF/LEF:TLE

tetramer:HDAC1
ArrowR-HSA-4641231 (Reactome)
'canonical' WNT

target genes:TCF/LEF:TLE

tetramer:HDAC1
TBarR-HSA-5229348 (Reactome)
'canonical' WNT

target

genes:TCF/LEF
ArrowR-HSA-8944352 (Reactome)
'canonical' WNT

target

genes:TCF/LEF
R-HSA-8944349 (Reactome)
'canonical' WNT

target gene

transcripts
ArrowR-HSA-5229348 (Reactome)
'canonical' WNT target genesR-HSA-5229348 (Reactome)
'canonical' WNT target genesR-HSA-8944352 (Reactome)
26S proteasomemim-catalysisR-HSA-2130282 (Reactome)
ADPArrowR-HSA-195275 (Reactome)
ADPArrowR-HSA-195283 (Reactome)
ADPArrowR-HSA-195287 (Reactome)
ADPArrowR-HSA-195300 (Reactome)
ADPArrowR-HSA-195318 (Reactome)
ADPArrowR-HSA-5229343 (Reactome)
AESR-HSA-4649028 (Reactome)
AMER1 geneR-HSA-5251557 (Reactome)
AMER1ArrowR-HSA-5251557 (Reactome)
AMER1R-HSA-195251 (Reactome)
APCR-HSA-5246693 (Reactome)
ATPR-HSA-195275 (Reactome)
ATPR-HSA-195283 (Reactome)
ATPR-HSA-195287 (Reactome)
ATPR-HSA-195300 (Reactome)
ATPR-HSA-195318 (Reactome)
ATPR-HSA-5229343 (Reactome)
AXIN1 geneR-HSA-5251555 (Reactome)
AXIN1ArrowR-HSA-5251555 (Reactome)
AXIN1R-HSA-195251 (Reactome)
AXIN:GSK3:CK1alpha:ub-APC:PP2A:AMER1 complexArrowR-HSA-195251 (Reactome)
AXIN:GSK3:CK1alpha:ub-APC:PP2A:AMER1 complexR-HSA-5229343 (Reactome)
AXIN:GSK3:CK1alpha:ub-APC:PP2A:AMER1 complexmim-catalysisR-HSA-5229343 (Reactome)
BTRC:CUL1:RBX1:SKP1ArrowR-HSA-2130282 (Reactome)
BTRC:CUL1:RBX1:SKP1R-HSA-2130279 (Reactome)
CSNK1A1R-HSA-195251 (Reactome)
CTBPsR-HSA-5334050 (Reactome)
CTNNB1:p-AXIN:GSK3:CK1alpha:ub-APC:PP2A:AMER1 complexArrowR-HSA-195304 (Reactome)
CTNNB1:p-AXIN:GSK3:CK1alpha:ub-APC:PP2A:AMER1 complexR-HSA-195318 (Reactome)
CTNNB1:p-AXIN:GSK3:CK1alpha:ub-APC:PP2A:AMER1 complexmim-catalysisR-HSA-195318 (Reactome)
CTNNB1R-HSA-195304 (Reactome)
FRAT1,2:GSK3betaTBarR-HSA-195283 (Reactome)
FRAT1,2:GSK3betaTBarR-HSA-195287 (Reactome)
FRAT1,2:GSK3betaTBarR-HSA-195300 (Reactome)
GSK3BR-HSA-195251 (Reactome)
HDAC1R-HSA-4641231 (Reactome)
K63polyUb-APCArrowR-HSA-5246693 (Reactome)
K63polyUb-APCR-HSA-195251 (Reactome)
K63polyUb-APCR-HSA-6781905 (Reactome)
K63polyUbR-HSA-5246693 (Reactome)
PP2AR-HSA-195251 (Reactome)
R-HSA-195251 (Reactome) The exact composition of the destruction complex is not known. A number of components appear to form a core complex, while others may associate with the complex transiently when a Wnt signal is present (reviewed in Kimelman and Xu, 2006). The core components include Axin, glycogen synthase kinase 3 (GSK-3), Casein kinase 1 (CKI) alpha, beta-catenin, Protein phosphatase 2A (PP2A) and Adenomatous Polyposis Coli (APC). CK1 epsilon, Diversin and PP1 may also be components of the complex.
R-HSA-195275 (Reactome) APC is phosphorylated on the 20 aa repeats by CK1 and potentially GSK-3. This significantly increases the binding affinity of the APC 20 aa repeats for beta-catenin, causing one of them to bind b-catenin in the same region as beta-catenin binds Axin, thus displacing beta-catenin from Axin ( Step 5 above) (Reviewed in Kimelman, 2006).
R-HSA-195280 (Reactome) The phosphorylation of the 20 aa repeats in APC results in an increase in affinity for beta-catenin (Ha et al., 2004, Xing et al., 2004; Liu et al., 2006). The binding site of phospho -(20 aa) APC on beta-catenin overlaps the binding site of Axin on beta catenin. In addition, phosphorylated APC prevents the association of Axin with beta-catenin (Ha et al., 2004, Xing et al., 2004). In this model, phosphorylated APC may compete with Axin for beta-catenin binding, resulting in dissociation of the Axin:beta-catenin interaction in the destruction complex (see Kimelman and Xu 2006).
R-HSA-195283 (Reactome) Phospho-(Ser45, Thr41) beta-catenin is phosphorylated by GSK3 at Ser37.
R-HSA-195287 (Reactome) Following CKI-mediated phosphorylation at Ser45, beta-catenin is phosphorylated by GSK3 at Thr41.
R-HSA-195300 (Reactome) Beta-catenin is then phosphorylated at Ser33. Phosphorylated S37 and S33 together with neighboring residues constitute the recognition motif for beta-TrCP.
R-HSA-195304 (Reactome) Beta-catenin associates with the destruction complex through an interaction with Axin and or APC. This association may also involve interactions with the 15 aa repeats in APC (Spink et al., 2001) or the third APC 20aa repeat and its N-terminal flanking residues (Ha et al., 2004, Xing et al., 2004; Liu et al., 2006).
R-HSA-195318 (Reactome) CK1a binds to Axin and phosphorylates beta-catenin at Ser45 priming GSK3 mediated phosphorylation at the more N-terminal residues (Amit et al., 2002; Liu et al., 2002; Yanagawa et al., 2002).
R-HSA-2130279 (Reactome) B-TrCP associates with phosphorylated beta-catenin through the B-TrCP WD40 repeat region. Currently, it is unclear whether the ubiquitin ligase binds beta-catenin after it leaves the complex. It is equally possible that it binds beta-catenin while beta-catenin is still bound to Axin.
R-HSA-2130282 (Reactome) Ubiquitinated beta-catenin is degraded by the proteasome.
R-HSA-2130286 (Reactome) Beta-catenin is ubiquitinated by the SCF-B-TrCP1 complex.
R-HSA-4641229 (Reactome) TCF1, LEF1, TCF3 and TCF4 are HMG box-containing DNA-binding proteins that recognize WNT-responsive elements (WREs) in the promoters of WNT target genes (reviewed in Brantjes et al, 2002). In the absence of a WNT signal, promoter-bound TCF/LEF is bound by one of four Groucho homologues, TLE1, 2, 3 or 4 (Levanon et al, 1998; Brantjes et al, 2001; Daniels and Weis, 2005). Groucho/TLE proteins are co-repressors for a variety of DNA-binding transcription factors and mediate repression at least in part through their interaction with histone deacetylases such as RPD3/HDAC1 (Arce et al, 2009; Brantjes et al, 2001; Chen et al, 1999; reviewed in Chen and Courey, 2000). Groucho proteins have been shown to homo-tetramerize through a glutamine rich Q domain at the N-terminus, and this oligomerization is required for repression. The Q domain is also sufficient for interaction with TCF/LEF proteins (Brantjes et al, 2001; Chen et al, 1998; Pinto and Lobe, 1996; Song et al, 2004). Studies with purified proteins have shown that human TLE1 and 2 bind to an amino-terminal truncated form of LEF1(69-397) with an affinity comparable to that for full length LEF1 (Daniels and Weis, 2005).
R-HSA-4641231 (Reactome) Groucho/TLE mediates repression of WNT target genes in part by recruiting a histone deacetlyase to the promoter. The weakly conserved central GP domain of Groucho/TLE has been shown to interact with the histone deacetylase RPD3/HDAC1 (Brantjes et al, 2001; Chen et al, 1999). Knockdown of rpd3 in Drosophila cells, or treatment of human or Drosophila cells with the histone deacetylase inhibitor Trichostatin A significantly decreases repression of a Groucho/TLE dependent reporter gene, and Groucho and RPD3 have been shown to co-localize to chromatin of target genes by ChIP leading to deacetylation of H3K9, H3K14, K4K5, H4K8 and H4K12 (Chen et al, 1999; Choi et al 1999; Winkler et al, 2010).
R-HSA-4649028 (Reactome) AES is a naturally occuring truncated form of TLE that contains only the Q and GP domain. AES has been shown to have a dominant negative effect on TLE-mediated repression (Miyasaka et al, 1993; Roose et al, 1998; Ren et al, 1999; Swingler et al, 2004). AES is believed to form oligomers with full length TLE proteins mediated by the Q domains; because AES is unable to interact with HDAC1, these oligomers are thought to be non-functional (Muhr et al, 2001; Brantjes et al, 2001).
R-HSA-5229343 (Reactome) In the absence of WNT signal, AXIN is a phosphoprotein; candidate kinases include both GSK3beta and CK1 (Ikeda et al, 1998; Willert et al, 1999; Jho et al, 1999; Yamamoto et al, 1999; Luo et al, 2007). Phosphorylation of AXIN is thought to increase its binding affinity for beta-catenin and GSK3beta, stabilizing the destruction complex and promoting efficient degradation of beta-catenin (Willert et al, 1999; Jho et al, 1999; Luo et al, 2007). A more recent model suggests that AXIN phosphorylation may disrupt an intramolecular interaction between its DIX domain and the beta-catenin binding region, which would otherwise keep AXIN in a 'closed' inactive state (Kim et al, 2013). Activation of the WNT pathway upon ligand binding favours dephosphorylation of AXIN by inactivating the kinases and allowing the steady state dephosphorylation by candidate phosphatases PP2A and PP1 to predominate (Willert et al, 1999; Luo et al, 2007; reviewed in Saito-Diaz et al, 2013).
R-HSA-5229348 (Reactome) Transcription of WNT genes is repressed in the absence of WNT signal by TLE:HDAC complexes (reviewed in Cinnamon and Paroush, 2008; Saito-Diaz et al, 2013). Represssion may also be mediated by CTBP proteins binding to TCF7L1 and TCF7L3 (Duval et al, 2000; Cuilliere-Dartigues et al, 2006; Tang et al, 2008).
R-HSA-5246693 (Reactome) In unstimulated cells, APC is K63 polyubiquitinated in a manner that depends on its association with AXIN. Although the precise timing of APC polyubiquitination is unclear, it is disrupted by abrogation of GSK3 kinase activity and in the presence of phosphodegron mutants of beta-catenin, suggesting that the formation of a functional destruction complex is required. Destruction complex formation is also dependent upon AXIN levels, which may be regulated at least in part by the balance of its ubiquitination and sumoylation (Kim et al, 2008).
Upon WNT3A stimulation, APC K63 polyubiquitination is lost coincident with disruption of the APC-AXIN interaction (Tran and Polakis, 2012). Interestingly, another study has shown that DVL is K63 polyubiquitinated upon WNT signaling (Tauriello et al, 2010), suggesting a possible model in which WNT signaling promotes a change in AXIN-K63 polyubiquitin binding partner to destabilize the destruction complex and promote pathway activation. Alternately, APC K63 polyubiquitination may protect beta-catenin from PP2A-mediated dephosphorylation and thus favour its degradation (Su et al, 2008).
R-HSA-5251555 (Reactome) AXIN1 was first identified as the product of the mouse gene fused and has since been shown to have a key role in the degradation of beta-catenin by the destruction complex (Zeng et al, 1997; reviewed in Saito-Diaz et al, 2013). Deletion, missense and nonsense mutations that lead to activated WNT signaling have been identified in the AXIN1 gene in human cancers, making AXIN1 a tumor suppressor gene (reviewed in Salahshor and Woodgett, 2005).
R-HSA-5251557 (Reactome) AMER1 was identified as a gene mutated in a subset of Wilms tumors (Rivera et al, 2007) and the protein has been shown to be a component of the beta-catenin destruction complex (Major et al, 2007).
R-HSA-5334050 (Reactome) In addition to repressing WNT-dependent targets through Groucho/TLE proteins, some TCF/LEF transcription factors may also work by recruiting the CTBP1 and CTBP2 repressors (Duval et al, 2000). CTBP-binding regions are present in the 'E-form' splice variants of TCF7L2 and in TCF7L1 and in vitro interactions have been demonstrated in Xenopus and mammals, although the in vivo relevance of these interactions is unclear (Brannon et al, 1999; Valenta et al, 2003; Cuilliere-Dartigues et al, 2006; Tang et al, 2008; Hamada and Bienz, 2004). Abrogation of the interaction interface results in a loss of TCF-CTBP colocalization and increased expression of a TCF-dependent reporter gene (Cuilliere-Dartigues et al, 2006; Tang et al, 2008).
R-HSA-6781905 (Reactome) ZRANB1 (Trabid) binds and cleaves K63-linked ubiquitin chains. It is required for efficient TCF-mediated transcription in cells with high Wnt pathway activity, including colorectal cancer cell lines. ZRANB1 can deubiquitinate the APC tumor suppressor protein, a negative regulator of Wnt-mediated transcription (Tran et al. 2008).
R-HSA-8944349 (Reactome) In the absence of a WNT signal, promoter-bound TCF/LEF is bound by one of four Groucho homologues, TLE1, 2, 3 or 4 (Levanon et al, 1998; Brantjes et al, 2001; Daniels and Weis, 2005). Groucho/TLE proteins are co-repressors for a variety of DNA-binding transcription factors and mediate repression at least in part through their interaction with histone deacetylases such as RPD3/HDAC1 (Arce et al, 2009; Brantjes et al, 2001; Chen et al, 1999; reviewed in Chen and Courey, 2000). Groucho proteins have been shown to homo-tetramerize through a glutamine rich Q domain at the N-terminus, and this oligomerization is required for repression. The Q domain is also sufficient for interaction with TCF/LEF proteins (Brantjes et al, 2001; Chen et al, 1998; Pinto and Lobe, 1996; Song et al, 2004). Studies with purified proteins have shown that human TLE1 and 2 bind to an amino-terminal truncated form of LEF1(69-397) with an affinity comparable to that for full length LEF1 (Daniels and Weis, 2005)

R-HSA-8944352 (Reactome) TCF7 (TCF1), LEF1, TCF7L1 (TCF3) and TCF7L2 (TCF4) are HMG box-containing DNA-binding proteins that recognize WNT-responsive elements (WREs) in the promoters of WNT target genes. The WRE consensus sequence is CCTTTGWW, where W represents either T or A (reviewed in Brantjes et al, 2002). In the absence of a WNT signal, promoter-bound TCF/LEF is bound by one of four Groucho homologues, TLE1, 2, 3 or 4 (Levanon et al, 1998; Brantjes et al, 2001; Daniels and Weis, 2005). Groucho/TLE proteins are co-repressors for a variety of DNA-binding transcription factors and mediate repression at least in part through their interaction with histone deacetylases such as RPD3/HDAC1 (Arce et al, 2009; Brantjes et al, 2001; Chen et al, 1999; reviewed in Chen and Courey, 2000).
RBX1:SKP1:CUL1:beta-TrCP1:phosphorylated beta-catenin complexArrowR-HSA-2130279 (Reactome)
RBX1:SKP1:CUL1:beta-TrCP1:phosphorylated beta-catenin complexR-HSA-2130286 (Reactome)
TCF/LEFR-HSA-8944352 (Reactome)
TCF7L2/TCF7L1:CTBPsArrowR-HSA-5334050 (Reactome)
TCF7L2/TCF7L1:CTBPsTBarR-HSA-5229348 (Reactome)
TCF7L2/TCF7L1R-HSA-5334050 (Reactome)
TLE tetramerArrowR-HSA-4641229 (Reactome)
TLE tetramerR-HSA-8944349 (Reactome)
TLE:AESArrowR-HSA-4649028 (Reactome)
TLER-HSA-4641229 (Reactome)
TLER-HSA-4649028 (Reactome)
UbArrowR-HSA-2130282 (Reactome)
UbR-HSA-2130286 (Reactome)
ZRANB1:K63polyUb-APCArrowR-HSA-6781905 (Reactome)
ZRANB1R-HSA-6781905 (Reactome)
p-AXIN:CK1alpha:GSK3B:phospho-APC (20 aa repeat region):PP2A:AMER1 complexArrowR-HSA-2130282 (Reactome)
p-AXIN:GSK3:CK1alpha:ub-APC:PP2A:AMER1 complexArrowR-HSA-5229343 (Reactome)
p-AXIN:GSK3:CK1alpha:ub-APC:PP2A:AMER1 complexR-HSA-195304 (Reactome)
p-S33,S37,T41,S45 CTNNB1:p-AXIN:CK1alpha:GSK3B:phospho-ub-APC (20 aa repeat region):PP2A:AMER1 complexArrowR-HSA-195275 (Reactome)
p-S33,S37,T41,S45 CTNNB1:p-AXIN:CK1alpha:GSK3B:phospho-ub-APC (20 aa repeat region):PP2A:AMER1 complexArrowR-HSA-195280 (Reactome)
p-S33,S37,T41,S45 CTNNB1:p-AXIN:CK1alpha:GSK3B:phospho-ub-APC (20 aa repeat region):PP2A:AMER1 complexR-HSA-195280 (Reactome)
p-S33,S37,T41,S45 CTNNB1:p-AXIN:CK1alpha:GSK3B:phospho-ub-APC (20 aa repeat region):PP2A:AMER1 complexR-HSA-2130279 (Reactome)
p-S33,S37,T41,S45-beta-catenin:p-AXIN:GSK3:CK1alpha:ub-APC:PP2A:AMER1 complexArrowR-HSA-195300 (Reactome)
p-S33,S37,T41,S45-beta-catenin:p-AXIN:GSK3:CK1alpha:ub-APC:PP2A:AMER1 complexR-HSA-195275 (Reactome)
p-S33,S37,T41,S45-beta-catenin:p-AXIN:GSK3:CK1alpha:ub-APC:PP2A:AMER1 complexmim-catalysisR-HSA-195275 (Reactome)
p-S37,T41,S45 CTNNB1:p-AXIN:GSK3:CK1alpha:ub-APC:PP2A:AMER1 complexArrowR-HSA-195283 (Reactome)
p-S37,T41,S45 CTNNB1:p-AXIN:GSK3:CK1alpha:ub-APC:PP2A:AMER1 complexR-HSA-195300 (Reactome)
p-S37,T41,S45 CTNNB1:p-AXIN:GSK3:CK1alpha:ub-APC:PP2A:AMER1 complexmim-catalysisR-HSA-195300 (Reactome)
p-S45 CTNNB1:p-Axin:GSK3:CK1alpha:ub-APC:PP2A:AMER1 complexArrowR-HSA-195318 (Reactome)
p-S45 CTNNB1:p-Axin:GSK3:CK1alpha:ub-APC:PP2A:AMER1 complexR-HSA-195287 (Reactome)
p-S45 CTNNB1:p-Axin:GSK3:CK1alpha:ub-APC:PP2A:AMER1 complexmim-catalysisR-HSA-195287 (Reactome)
p-T41,S45 CTNNB1:p-AXIN:GSK3:CK1alpha:ub-APC:PP2A:AMER1 complexArrowR-HSA-195287 (Reactome)
p-T41,S45 CTNNB1:p-AXIN:GSK3:CK1alpha:ub-APC:PP2A:AMER1 complexR-HSA-195283 (Reactome)
p-T41,S45 CTNNB1:p-AXIN:GSK3:CK1alpha:ub-APC:PP2A:AMER1 complexmim-catalysisR-HSA-195283 (Reactome)
ubiquitinated phospho-beta-catenin:RBX1:SCF(beta-TrCP1) complexArrowR-HSA-2130286 (Reactome)
ubiquitinated phospho-beta-catenin:RBX1:SCF(beta-TrCP1) complexR-HSA-2130282 (Reactome)
unknown ubiquitin ligasemim-catalysisR-HSA-5246693 (Reactome)
Personal tools