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

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91581011, 134, 6, 7551222PP2A SCF-beta-TrCP1 complex associated with phosphorylated beta-catenin PP2A pS45- beta-catenin cytosolAxinGSK3CK1alphaAPCPP2AFAM123B complex SCF-beta-TrCP1 complex associated with phosphorylated beta-catenin AxinGSK3CK1alphaAPCPP2AFAM123B complex PP2A PP2A p-T41,S45-beta catenin PP2A PP2A p-S33,S37,T41,S45-beta-catenin AxinGSK3CK1alphaAPCPP2AFAM123B complex AxinGSK3CK1alphaAPCPP2AFAM123B complex 26S proteasome PP2A SCF-beta-TrCP1 complex beta-cateninAxinGSK3CK1alphaAPCPP2AFAM123B complex SCF-beta-TrCP1 complex FRAT1 or FRAT2 PP2A p-S33,S37,T41,S45-beta-cateninAxinGSK3CK1alphaAPCPP2AFAM123B complex p-S33,S37,T41,S45-beta-catenin p-S33,S37,T41,S45-beta-catenin ubiquitinated phospho-beta-cateninSCFbeta-TrCP1 complex p-S33,S37,T41,S45-beta-cateninAxinCK1alphaGSK3Bphospho-APC AxinGSK3CK1alphaAPCPP2AFAM123B complex p-S33,S37,T41,S45-beta-cateninAxinCK1alphaGSK3Bphospho-APC p-T41,S45-beta-cateninAxinGSK3CK1alphaAPCPP2AFAM123B complex FRAT1/FRAT2GSK3beta Complex PP2A PP2A PP2A AxinGSK3CK1alphaAPCPP2AFAM123B complex p-S33,S37,T41,S45-beta-catenin SCF-beta-TrCP1 complex p-S33,S37,T41,S45-beta-catenin Ub p-S37,T41,S45-beta-cateninAxin,GSK3CK1alphaAPCPP2AFAM123B complex PP2A pS45-beta-cateninAxinGSK3CK1alphaAPCPP2AFAM123B complex p-S33,S37,T41,S45-beta-cateninAxinCK1alphaGSK3Bphospho-APC p-S37,T41,S45-beta-catenin p-S33,S37,T41,S45-beta-cateninAxinCK1alphaGSK3Bphospho-APC AxinCK1alphaGSK3Bphospho-APC CSNK1A1p-T41,S45-beta-cateninAxinGSK3CK1alphaAPCPP2AFAM123B complexPSMD12 PSMB8 ATPAMER1 GSK3B CSNK1A1PSMC1GSK3B PSMB4 UBCADPCSNK1A1AXIN1 PSMD5 CSNK1A1p-S33,S37,S45,T41-CTNNB1-1 APC p-APC p-S37,T41,S45-beta-cateninAxin,GSK3CK1alphaAPCPP2AFAM123B complex26S proteasomeADPUBCCSNK1A1p-S45,T41-CTNNB1-1 GSK3B p-APC PSMA7PSMB7 AMER1CSNK1A1AMER1 UBCUBCGSK3B APC PSMA4 PSMD7PSMB3 UBBPSMA2 CSNK1A1UBBFRAT1 GSK3B PSMB2 BTRC PSMA3 AXIN1PSME4 RPS27APSMD10 PP2Ap-S33,S37,S45,T41-CTNNB1-1 ADPAPC GSK3B PSMC6p-S33,S37,T41,S45-beta-cateninAxinCK1alphaGSK3Bphospho-APC ADPGSK3B CSNK1A1AXIN1 AMER1 APC PSMB10 UBCPSMC2 PSMD4UBCp-S33,S37,S45,T41-CTNNB1-1 p-S33,S37,S45,T41-CTNNB1-1 ATPPSMB6 FRAT1/FRAT2GSK3beta ComplexPSMD3 GSK3B beta-cateninp-APC PSMB1 ATPATPAPCPSMD9 UBCAMER1 CSNK1A1GSK3B AMER1 APC UBA52PSMD14 UBCPSMC4 ATPAXIN1 p-S45-CTNNB1-1 UBCAXIN1 AXIN1 CSNK1A1GSK3B BTRC p-APC AMER1 AxinCK1alphaGSK3Bphospho-APC PSMD2 GSK3B PSMD11 AMER1 APC PSME3 AXIN1 beta-cateninAxinGSK3CK1alphaAPCPP2AFAM123B complexCUL1 p-APC CUL1 ubiquitinated phospho-beta-cateninSCFbeta-TrCP1 complexCSNK1A1AXIN1 PSMC3 PSMA6 GSK3BPSMD6pS45-beta-cateninAxinGSK3CK1alphaAPCPP2AFAM123B complexCUL1 p-S33,S37,S45,T41-CTNNB1-1 UBBGSK3B SKP1 CTNNB1-1 AXIN1 PSME1 PSMF1ADPAXIN1 PSMA1 PSMD13 p-S33,S37,T41,S45-beta-cateninAxinCK1alphaGSK3Bphospho-APC AMER1 SCF-beta-TrCP1 complexPSMB11 AxinGSK3CK1alphaAPCPP2AFAM123B complexBTRC PSMA8 p-S33,S37,T41,S45-beta-cateninAxinGSK3CK1alphaAPCPP2AFAM123B complexAMER1 AXIN1 PSMD1 PSMB5 AMER1 PSMD8 p-S37,S45,T41-CTNNB1-1 SCF-beta-TrCP1 complex associated with phosphorylated beta-cateninAXIN1 SKP1 PSME2 UbPSMA5 PSMB9 AMER1 FRAT2 SKP1 CSNK1A1PSMC5 3, 121314


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Wikipathways-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).

Original Pathway at Reactome: http://www.reactome.org/PathwayBrowser/#DB=gk_current&FOCUS_SPECIES_ID=48887&FOCUS_PATHWAY_ID=195253

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Bibliography

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  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

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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
26S proteasomeComplexREACT_2353 (Reactome)
ADPMetaboliteCHEBI:16761 (ChEBI)
AMER1 ProteinQ5JTC6 (Uniprot-TrEMBL)
AMER1ProteinQ5JTC6 (Uniprot-TrEMBL)
APC ProteinP25054 (Uniprot-TrEMBL)
APCProteinP25054 (Uniprot-TrEMBL)
ATPMetaboliteCHEBI:15422 (ChEBI)
AXIN1 ProteinO15169 (Uniprot-TrEMBL)
AXIN1ProteinO15169 (Uniprot-TrEMBL)
Axin

CK1alpha GSK3B

phospho-APC 		ComplexREACT_10381 (Reactome) In this complex Axin is bound to beta-catenin.
Axin

GSK3 CK1alpha APC PP2A

FAM123B complex		ComplexREACT_10218 (Reactome)
BTRC ProteinQ9Y297 (Uniprot-TrEMBL)
CSNK1A1ProteinP48729 (Uniprot-TrEMBL)
CTNNB1-1 ProteinP35222-1 (Uniprot-TrEMBL)
CUL1 ProteinQ13616 (Uniprot-TrEMBL)
FRAT1 ProteinQ92837 (Uniprot-TrEMBL)
FRAT1/FRAT2 GSK3beta ComplexComplexREACT_76688 (Reactome)
FRAT2 ProteinO75474 (Uniprot-TrEMBL)
GSK3B ProteinP49841 (Uniprot-TrEMBL)
GSK3BProteinP49841 (Uniprot-TrEMBL)
PP2AComplexREACT_10628 (Reactome)
PSMA1 ProteinP25786 (Uniprot-TrEMBL)
PSMA2 ProteinP25787 (Uniprot-TrEMBL)
PSMA3 ProteinP25788 (Uniprot-TrEMBL)
PSMA4 ProteinP25789 (Uniprot-TrEMBL)
PSMA5 ProteinP28066 (Uniprot-TrEMBL)
PSMA6 ProteinP60900 (Uniprot-TrEMBL)
PSMA7ProteinO14818 (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)
PSMC1ProteinP62191 (Uniprot-TrEMBL)
PSMC2 ProteinP35998 (Uniprot-TrEMBL)
PSMC3 ProteinP17980 (Uniprot-TrEMBL)
PSMC4 ProteinP43686 (Uniprot-TrEMBL)
PSMC5 ProteinP62195 (Uniprot-TrEMBL)
PSMC6ProteinP62333 (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)
PSMD4ProteinP55036 (Uniprot-TrEMBL)
PSMD5 ProteinQ16401 (Uniprot-TrEMBL)
PSMD6ProteinQ15008 (Uniprot-TrEMBL)
PSMD7ProteinP51665 (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)
PSMF1ProteinQ92530 (Uniprot-TrEMBL)
RPS27AProteinP62979 (Uniprot-TrEMBL)
SCF-beta-TrCP1 complex associated with phosphorylated beta-cateninComplexREACT_10593 (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.
SCF-beta-TrCP1 complexComplexREACT_6992 (Reactome)
SKP1 ProteinP63208 (Uniprot-TrEMBL)
UBA52ProteinP62987 (Uniprot-TrEMBL)
UBBProteinP0CG47 (Uniprot-TrEMBL)
UBCProteinP0CG48 (Uniprot-TrEMBL)
UbProteinREACT_3316 (Reactome)
beta-catenin

Axin GSK3 CK1alpha APC PP2A

FAM123B complex		ComplexREACT_10837 (Reactome)
beta-cateninProteinREACT_10304 (Reactome)
p-APC ProteinP25054 (Uniprot-TrEMBL)
p-S33,S37,S45,T41-CTNNB1-1 ProteinP35222-1 (Uniprot-TrEMBL)
p-S33,S37,T41,S45-beta-catenin

Axin CK1alpha GSK3B

phospho-APC 		ComplexREACT_10660 (Reactome) In this complex Axin is bound to beta-catenin.
p-S33,S37,T41,S45-beta-catenin

Axin CK1alpha GSK3B

phospho-APC 		ComplexREACT_10886 (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-beta-catenin

Axin GSK3 CK1alpha APC PP2A

FAM123B complex		ComplexREACT_10610 (Reactome)
p-S37,S45,T41-CTNNB1-1 ProteinP35222-1 (Uniprot-TrEMBL)
p-S37,T41,S45-beta-catenin

Axin,GSK3 CK1alpha APC PP2A

FAM123B complex		ComplexREACT_10861 (Reactome)
p-S45,T41-CTNNB1-1 ProteinP35222-1 (Uniprot-TrEMBL)
p-S45-CTNNB1-1 ProteinP35222-1 (Uniprot-TrEMBL)
p-T41,S45-beta-catenin

Axin GSK3 CK1alpha APC PP2A

FAM123B complex		ComplexREACT_10844 (Reactome)
pS45-beta-catenin

Axin GSK3 CK1alpha APC PP2A

FAM123B complex		ComplexREACT_10809 (Reactome)
ubiquitinated phospho-beta-catenin

SCF

beta-TrCP1 complex		ComplexREACT_10202 (Reactome)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
26S proteasomemim-catalysisREACT_10017 (Reactome)
ADPArrowREACT_9955 (Reactome)
ADPArrowREACT_9959 (Reactome)
ADPArrowREACT_9978 (Reactome)
ADPArrowREACT_9983 (Reactome)
ADPArrowREACT_9987 (Reactome)
AMER1REACT_10134 (Reactome)
APCREACT_10134 (Reactome)
ATPREACT_9955 (Reactome)
ATPREACT_9959 (Reactome)
ATPREACT_9978 (Reactome)
ATPREACT_9983 (Reactome)
ATPREACT_9987 (Reactome)
AXIN1REACT_10134 (Reactome)
Axin

CK1alpha GSK3B

phospho-APC 		ArrowREACT_10017 (Reactome)
Axin

GSK3 CK1alpha APC PP2A

FAM123B complex		REACT_10111 (Reactome)
CSNK1A1REACT_10134 (Reactome)
FRAT1/FRAT2 GSK3beta ComplexTBarREACT_9955 (Reactome)
FRAT1/FRAT2 GSK3beta ComplexTBarREACT_9959 (Reactome)
FRAT1/FRAT2 GSK3beta ComplexTBarREACT_9987 (Reactome)
GSK3BREACT_10134 (Reactome)
PP2AREACT_10134 (Reactome)
REACT_10017 (Reactome) Ubiquitinated beta-catenin is degraded by the proteasome.
REACT_10082 (Reactome) Beta-catenin is ubiquitinated by the SCF-B-TrCP1 complex.
REACT_10111 (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).
REACT_10127 (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).
REACT_10134 (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.
REACT_9955 (Reactome) Following CKI-mediated phosphorylation at Ser45, beta-catenin is phosphorylated by GSK3 at Thr41.
REACT_9959 (Reactome) Phospho-(Ser45, Thr41) beta-catenin is phosphorylated by GSK3 at Ser37.
REACT_9977 (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.
REACT_9978 (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).
REACT_9983 (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).
REACT_9987 (Reactome) Beta-catenin is then phosphorylated at Ser33. Phosphorylated S37 and S33 together with neighboring residues constitute the recognition motif for beta-TrCP.
SCF-beta-TrCP1 complex associated with phosphorylated beta-cateninREACT_10082 (Reactome)
SCF-beta-TrCP1 complexArrowREACT_10017 (Reactome)
SCF-beta-TrCP1 complexREACT_9977 (Reactome)
UbArrowREACT_10017 (Reactome)
UbREACT_10082 (Reactome)
beta-catenin

Axin GSK3 CK1alpha APC PP2A

FAM123B complex		REACT_9978 (Reactome)
beta-catenin

Axin GSK3 CK1alpha APC PP2A

FAM123B complex		mim-catalysisREACT_9978 (Reactome)
beta-cateninREACT_10111 (Reactome)
p-S33,S37,T41,S45-beta-catenin

Axin CK1alpha GSK3B

phospho-APC 		ArrowREACT_9983 (Reactome)
p-S33,S37,T41,S45-beta-catenin

Axin CK1alpha GSK3B

phospho-APC 		REACT_9977 (Reactome)
p-S33,S37,T41,S45-beta-catenin

Axin GSK3 CK1alpha APC PP2A

FAM123B complex		ArrowREACT_9987 (Reactome)
p-S33,S37,T41,S45-beta-catenin

Axin GSK3 CK1alpha APC PP2A

FAM123B complex		REACT_9983 (Reactome)
p-S33,S37,T41,S45-beta-catenin

Axin GSK3 CK1alpha APC PP2A

FAM123B complex		mim-catalysisREACT_9983 (Reactome)
p-S37,T41,S45-beta-catenin

Axin,GSK3 CK1alpha APC PP2A

FAM123B complex		ArrowREACT_9959 (Reactome)
p-S37,T41,S45-beta-catenin

Axin,GSK3 CK1alpha APC PP2A

FAM123B complex		REACT_9987 (Reactome)
p-S37,T41,S45-beta-catenin

Axin,GSK3 CK1alpha APC PP2A

FAM123B complex		mim-catalysisREACT_9987 (Reactome)
p-T41,S45-beta-catenin

Axin GSK3 CK1alpha APC PP2A

FAM123B complex		ArrowREACT_9955 (Reactome)
p-T41,S45-beta-catenin

Axin GSK3 CK1alpha APC PP2A

FAM123B complex		REACT_9959 (Reactome)
p-T41,S45-beta-catenin

Axin GSK3 CK1alpha APC PP2A

FAM123B complex		mim-catalysisREACT_9959 (Reactome)
pS45-beta-catenin

Axin GSK3 CK1alpha APC PP2A

FAM123B complex		ArrowREACT_9978 (Reactome)
pS45-beta-catenin

Axin GSK3 CK1alpha APC PP2A

FAM123B complex		REACT_9955 (Reactome)
pS45-beta-catenin

Axin GSK3 CK1alpha APC PP2A

FAM123B complex		mim-catalysisREACT_9955 (Reactome)
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