Identifiers
adenomatous polyposis coli
HUGO:APC, HGNC:583, ENTREZ:324, UNIPROT:P25054??, GENECARDS:GC05P112101
HUGO:APC HGNC:583 ENTREZ:324 UNIPROT:P25054 GENECARDS:APC REACTOME:403429 KEGG:5624 ATLASONC:APC118 WIKI:APC
"adenomatosis polyposis coli"
Maps_Modules
HMC:ACTIVATING_INVASION_AND_METASTASIS
EMT Senescence / EMT_REGULATORS
EMT Senescence / CELL_CELL_ADHESIONS
EMT Senescence / ADHERENS_JUNCTIONS
HMC:EVADING_GROWTH_SUPPRESSORS
Survival / WNT_CANONICAL
Survival / WNT_NON_CANONICAL
References
PMID:19751508
PMID:22270359
PMID:16940750
in the absence of Wnt ligands, b-catenin is phosphorylated by CK1 and GSK-3 in the context of a destruction complex with APC and Axin.
Phosphorylated b-catenin is consequently targeted for ubiquitination and degraded.
Upon ligand binding (right panel), DVL1 (dishevelled) recruits the Axin-GSK-3 complex, resulting in the sequential phosphorylation of LRP6 by CK1 and GSK-3.
Phoshorylated LRP6 serves as a docking site for additional Axin-GSK-3 complex, resulting in the disassembly of the destruction complex.
Non phosphorylated and thus stabilized b-catenin translocates to the nucleus where it activates transcription of target genes together with LEF/TCFs
PMID:20006983
References
em_emtc_emtc_re1011( EMT Senescence ):
PMID:10581160
PMID:17318175
PMID:10421629
Recruitment of CTNNB1 via the degradation complex of APC/AXIN1 is regulated by a series of ordered phosphorylation events.
Phosphorylation of AXIN1 by CSNK1 (casein kinase 1) and GSK3B can increase axin binding to CTNNB1.
PMID:8638126
PMID:11487578
PMID:15327768
AXIN1 also promotes phosphorylation of APC by CSNK1 and GSK3B.
Phosphorylated APC has higher affinity to CTNNB1.
PMID:12554650
Finally, these phosphorylation events allo CTNNB1 to be a more efficient substrate of both CSNK1 (at S45) and the GSK3B (at T41, S33, S37).
The affinity of phosphorylated APC to CTNNB1 is higher than that of phosphorylated AXIN1.
Therefore upon phosphorylation, APC can displace AXIN1 from CTNNB1, allowing AXIN1 to bind another molecule of CTNNB1.
References
su_wca1_s_wca1_re74:( Survival ) PMID:21498506 PMID:17925382
su_wca1_s_wca3_re84:( Survival ) PMID:10984057
su_wnc1_s_wnc4_re34( Survival ):
Unknown which amino acid residue
PMID:22399895
su_wnc1_s_wnc4_re36:( Survival ) PMID:22898821,
su_wnc1_s_wnc4_re39( Survival ):
Positive modulaion
PMID:15755874, PMID:23308069
su_wnc1_s_wnc4_re40:( Survival ) PMID:19900451
su_wnc1_s_wnc4_re45:( Survival ) PMID:17588722
su_wca1_s_wca1_re34( Survival ):
PMID:21498506
Membrane-bound AMER1 acts as scaffold and brings APC to the membrane
su_wca1_s_wca2_re64( Survival ):
HECTD1 KO disrupts APC-AXIN interaction and augments WNT3a-induced signaling
PMID:23277359 PMID:22761442
su_wca1_s_wca3_re75:( Survival ) PMID:11972058
su_wca1_s_wca3_re77( Survival ):
The C-terminus of APC inhibits activity of the CK2 enzyme
PMID:11972058
su_wca1_s_wca3_re78( Survival ):
Site is adjacent to the NLS2 in APC
PMID:11689703
su_wca1_s_wca3_re90:( Survival ) PMID:11585828
References
s_wnc4_re34( Survival ):
Unknown which amino acid residue
PMID:22399895
References
s_wca1_re74:( Survival ) PMID:21498506 PMID:17925382
s_wca3_re84:( Survival ) PMID:10984057
s_wca1_re34( Survival ):
PMID:21498506
Membrane-bound AMER1 acts as scaffold and brings APC to the membrane
s_wca2_re64( Survival ):
HECTD1 KO disrupts APC-AXIN interaction and augments WNT3a-induced signaling
PMID:23277359 PMID:22761442
s_wca3_re75:( Survival ) PMID:11972058
s_wca3_re77( Survival ):
The C-terminus of APC inhibits activity of the CK2 enzyme
PMID:11972058
s_wca3_re78( Survival ):
Site is adjacent to the NLS2 in APC
PMID:11689703
s_wca3_re90:( Survival ) PMID:11585828
s_wnc4_re34( Survival ):
Unknown which amino acid residue
PMID:22399895
s_wnc4_re36:( Survival ) PMID:22898821,
s_wnc4_re39( Survival ):
Positive modulaion
PMID:15755874, PMID:23308069
s_wnc4_re40:( Survival ) PMID:19900451
s_wnc4_re45:( Survival ) PMID:17588722
Maps_Modules
HMC:EVADING_GROWTH_SUPPRESSORS
Survival / WNT_CANONICAL
Maps_Modules
HMC:EVADING_GROWTH_SUPPRESSORS
Survival / WNT_CANONICAL
References
s_wca2_re64( Survival ):
HECTD1 KO disrupts APC-AXIN interaction and augments WNT3a-induced signaling
PMID:23277359 PMID:22761442
s_wca2_re65( Survival ):
Ubiquitination increases binding of APC with AXIN.
PMID:23277359
References
s_wca3_re78( Survival ):
Site is adjacent to the NLS2 in APC
PMID:11689703
s_wca3_re85:( Survival ) PMID:10984057
s_wca3_re91:( Survival ) PMID:11585828
References
s_wca3_re93:( Survival ) Not known if this dissociation occurs (here or later)
s_wca3_re85:( Survival ) PMID:10984057
s_wca3_re88:( Survival ) PMID:10984057 PMID:11263497
References
s_wca3_re80:( Survival ) PMID:11689703
References
s_wca3_re94:( Survival ) Not known if this dissociation occurs (here or later)
s_wca3_re81:( Survival ) PMID:18744248
s_wca3_re84:( Survival ) PMID:10984057
s_wca3_re89:( Survival ) PMID:10984057 PMID:11263497
s_wca3_re95:( Survival ) PMID:22787431
s_wca3_re104:( Survival ) PMID:15525529
+ APC@Cytosol → APC:AXIN1@Cytosol
→ (APC|pho:AXIN1|pho)|active@Cytosol
→ APC:AXIN1@Cytosol
+ (APC|pho:AXIN1|pho)|active@Cytosol → APC|pho:AXIN1|pho:_beta_-Catenin*@Cytosol
→ APC@Cytosol
→ APC|pho:AXIN1|pho:_beta_-Catenin*|pho|pho|pho|pho@Cytosol
→ degraded
→ APC|pho:AXIN1|pho:_beta_-Catenin*|pho@Cytosol
+ _beta_-Catenin*@Cytoplasm → AMER1*:APC:AXIN*|S80_pho|S82_pho|S222_pho|S473_pho|S614_pho|S621_pho:CK1_alpha_*:GSK3*:PtdIns(4,5)-P2:_beta_-Catenin*@Cytoplasm
→ AMER1*:APC|S1505_pho|S1501_pho|S1504_pho|S1507_pho|S1503_pho|S1510_pho:AXIN*|S80_pho|S82_pho|S222_pho|S473_pho|S614_pho|S621_pho:CK1_alpha_*:GSK3*:PtdIns(4,5)-P2:_beta_-Catenin*|S45_pho|T41_pho|S37_pho|S33_pho@Cytoplasm
→ AMER1*:APC:AXIN*|S80_pho|S82_pho|S222_pho|S473_pho|S614_emp|S621_pho:CK1_alpha_*:GSK3*:PtdIns(4,5)-P2@Cytoplasm
→ AMER1*:APC:AXIN*|S80_pho|S82_pho|S222_pho|S473_pho|S614_pho|S621_pho:CK1_alpha_*:GSK3*:PtdIns(4,5)-P2@Cytoplasm
+ PPP1C*:PPP1R*@Cytoplasm → AMER1*:APC:AXIN*|S80_pho|S82_pho|S222_pho|S473_pho:CK1_alpha_*:GSK3*:PPP1C*:PPP1R*@Cytoplasm
→ APC:AXIN*|S80_emp|S82_emp|S222_emp|S473_emp:CK1_alpha_*:GSK3*:PPP1C*:PPP1R*@Cytoplasm
→ GSK3*@Cytoplasm + AMER1*:APC:AXIN*:CK1_alpha_*:GSK3*:PtdIns(4,5)-P2@Cytoplasm + PPP1C*:PPP1R*@Cytoplasm
→ AMER1*:APC:AXIN*|S80_pho|S82_pho|S222_pho|S473_pho|S614_pho|S621_pho:CK1_alpha_*:GSK3*:PtdIns(4,5)-P2:_beta_-Catenin*|S45_pho@Cytoplasm
+ PP2A_C*:PR55_alpha_*:PR65_A*@Cytoplasm → AMER1*:APC:AXIN*|S80_pho|S82_pho|S222_pho|S473_pho|S614_pho|S621_pho:CK1_alpha_*:GSK3*:PP2A_C*:PR55_alpha_*:PR65_A*:_beta_-Catenin*|S45_pho|T41_pho|S37_pho|S33_pho@Cytoplasm
→ APC:AXIN*|S80_pho|S82_pho|S222_pho|S473_pho|S614_pho|S621_pho:CK1_alpha_*:GSK3*:PP2A_C*:PR55_alpha_*:PR65_A*:_beta_-Catenin*|S45_emp|T41_emp|S37_emp|S33_emp@Cytoplasm
→ PP2A_C*:PR55_alpha_*:PR65_A*@Cytoplasm + _beta_-Catenin*@Cytoplasm + AMER1*:APC:AXIN*|S80_pho|S82_pho|S222_pho|S473_pho|S614_pho|S621_pho:CK1_alpha_*:GSK3*:PtdIns(4,5)-P2@Cytoplasm
→ AMER1*:APC:AXIN*|S80_pho|S82_pho|S222_pho|S473_pho|S614_pho|S621_pho:CK1_alpha_*:GSK3*:PtdIns(4,5)-P2:_beta_-Catenin*|S45_pho|T41_pho@Cytoplasm
+ APC@Cytoplasm + AMER1*@Cytoplasm → AMER1*:APC:AXIN*:CK1_alpha_*:GSK3*:PtdIns(4,5)-P2@Cytoplasm
→ AMER1*:APC:AXIN*:CK1_alpha_*:CK1_epsilon_*:CK1_gamma_*:DVL*|pho|pho|pho:E-Cadherin*:FZD*:GSK3*:G_alpha_o*:G_beta_*:G_gamma_*:LRP5_6*|T1479_pho|S1490_pho|T1493_pho|S1496_pho:PRR*:WNT*:_beta_-Arrestin2*:p120*@Endosome
→ AMER1*:APC:AXIN*|S80_pho|S82_pho|S222_pho|S473_pho|S614_pho|S621_pho:CK1_alpha_*:GSK3*:PtdIns(4,5)-P2:_beta_-Catenin*|S45_pho|T41_pho|S37_pho@Cytoplasm
→ AMER1*:APC:AXIN*|S80_pho|S82_pho|S222_pho|S473_pho:CK1_alpha_*:GSK3*:PtdIns(4,5)-P2@Cytoplasm
+ CUL1:E1*:FAF*:NEDD8:RAD6*:RBX1:SKP*:_beta_TRCP*@Cytoplasm + CK2_alpha_'*:CK2_alpha_*:CK2_beta_*:CSN1*:CSN2*:CSN3*:CSN4*:CSN5*:CSN6*:CSN7*:CSN8*:PKD*:USP15@Cytoplasm → AMER1*:APC|S1505_pho|S1501_pho|S1504_pho|S1507_pho|S1503_pho|S1510_pho:AXIN*|S80_pho|S82_pho|S222_pho|S473_pho|S614_pho|S621_pho:CK1_alpha_*:CK2_alpha_'*:CK2_alpha_*:CK2_beta_*:CSN1*:CSN2*:CSN3*:CSN4*:CSN5*:CSN6*:CSN7*:CSN8*:CUL1:E1*:FAF*:GSK3*:NEDD8:PKD*:PtdIns(4,5)-P2:RAD6*:RBX1:SKP*:USP15:_beta_-Catenin*|S45_pho|T41_pho|S37_pho|S33_pho|K19_ubi|K49_ubi:_beta_TRCP*@Cytoplasm
→ CK2_alpha_'*:CK2_alpha_*:CK2_beta_*:CSN1*:CSN2*:CSN3*:CSN4*:CSN5*:CSN6*:CSN7*:CSN8*:CUL1:NEDD8:PKD*:RAD6*:RBX1:SKP*:USP15:_beta_TRCP*@Cytoplasm + APC|S1505_pho|S1501_ubi|S1504_pho|S1507_pho|S1503_pho|S1510_ubi:AXIN*|S80_pho|S82_pho|S222_pho|S473_pho|S614_pho|S621_pho@Cytoplasm + _beta_-Catenin*|S45_pho|T41_pho|S37_pho|S33_pho|K19_ubi|K49_ubi@Cytoplasm
→ AMER1*:APC:AXIN*|S80_pho|S82_pho|S222_pho|S473_pho|S614_pho|S621_pho:CK1_alpha_*:GSK3*:PtdIns(4,5)-P2:_beta_-Catenin*|S45_pho|T41_pho|S37_pho|S33_pho@Cytoplasm
→ AMER1*:APC|S1505_pho:AXIN*|S80_pho|S82_pho|S222_pho|S473_pho|S614_pho|S621_pho:CK1_alpha_*:GSK3*:PtdIns(4,5)-P2:_beta_-Catenin*|S45_pho|T41_pho|S37_pho|S33_pho@Cytoplasm
→ AMER1*:APC|S1505_pho|S1501_pho:AXIN*|S80_pho|S82_pho|S222_pho|S473_pho|S614_pho|S621_pho:CK1_alpha_*:GSK3*:PtdIns(4,5)-P2:_beta_-Catenin*|S45_pho|T41_pho|S37_pho|S33_pho@Cytoplasm
→ APC@Cytoplasm + Microtubules@Cytoplasm
→ Cell migration@Cytoplasm
→ AMER1*:APC|S1505_pho|S1501_pho|S1504_pho:AXIN*|S80_pho|S82_pho|S222_pho|S473_pho|S614_pho|S621_pho:CK1_alpha_*:GSK3*:PtdIns(4,5)-P2:_beta_-Catenin*|S45_pho|T41_pho|S37_pho|S33_pho@Cytoplasm
→ AMER1*:APC|S1505_pho|S1501_pho|S1504_pho|S1507_pho:AXIN*|S80_pho|S82_pho|S222_pho|S473_pho|S614_pho|S621_pho:CK1_alpha_*:GSK3*:PtdIns(4,5)-P2:_beta_-Catenin*|S45_pho|T41_pho|S37_pho|S33_pho@Cytoplasm
→ APC|K63_ubi@Cytoplasm
+ AXIN*:CK1_alpha_*:GSK3*@Cytoplasm → APC|K63_ubi:AXIN*:CK1_alpha_*:GSK3*@Cytoplasm
→ WNT canonical pathway@Cytoplasm
→ Degradation complex WNT canoncical pathway@Cytoplasm
+ CTBP*|hm2@Nucleus → APC:CTBP*|hm2@Nucleus
+ APC:CTBP*|hm2@Nucleus → APC:CTBP*|hm2:HDAC1_2*@Nucleus
→ APC|T1487_pho:CTBP*|hm2:HDAC1_2*@Nucleus
+ BCL9:DVL*:JUN|pho|pho:LEF_TCF*:PYGO*:WRE*:_beta_-Catenin*|K345_ace|ace@Nucleus → APC|T1487_pho:BCL9:CTBP*|hm2:DVL*:HDAC1_2*:JUN|pho|pho:LEF_TCF*:PYGO*:WRE*:_beta_-Catenin*|K345_ace|ace@Nucleus
→ APC|T1487_pho:_beta_-Catenin*|K345_ace|ace@Nucleus + su_wca1_s_wca3_s405 + CTBP*:HDAC1_2*:LEF_TCF*:WRE*@Nucleus + DVL*:JUN|pho|pho@Nucleus
→ APC|T1487_pho:_beta_-Catenin*|K345_ace|ace@Cytoplasm
→ Degradation complex WNT canoncical pathway@Cytoplasm
+ CK2_alpha_'*:CK2_alpha_*:CK2_beta_*@Cytoplasm → APC:CK2_alpha_'*:CK2_alpha_*:CK2_beta_*@Cytoplasm
→ APC:CK2_alpha_'*:CK2_alpha_*:CK2_beta_*@Cytoplasm
→ CK2_alpha_'*:CK2_alpha_*:CK2_beta_*@Cytoplasm
→ APC|S2034_pho@Cytoplasm
→ APC|S2034_pho:B56_alpha_*@Nucleus
→ APC|S2054_pho@Cytoplasm
→ DNA replication@Nucleus
→ APC:B56_alpha_*@Nucleus
→ APC@Cytoplasm
→ APC|S2034_pho@Cytoplasm
APC|S2034_pho:_beta_-Catenin*@Cytoplasm
APC:_beta_-Catenin*@Cytoplasm
+ APC|S2034_pho@Nucleus → su_wca1_s_wca3_s314
+ APC@Nucleus → su_wca1_s_wca3_s317
+ B56_alpha_*@Cytoplasm → APC:B56_alpha_*@Cytoplasm
+ B56_alpha_*@Cytoplasm → APC|S2034_pho:B56_alpha_*@Cytoplasm
→ B56_alpha_*@Nucleus + APC|S2034_pho@Nucleus
→ APC@Nucleus + B56_alpha_*@Nucleus
→ BER DNA Repair@Nucleus
→ Degradation complex WNT canoncical pathway@Cytoplasm
→ APC|pho@Cytoplasm
+ EB1*@Cytoplasm + APC@Cytoplasm → AMER2:APC:EB1*:PtdIns-(4,5)-P_sub_2@Cytoplasm
→ Microtubele polymerisation@Cytoplasm
→ APC_sub_TRUNC_endsub_*@Cytoplasm
+ HTID1_50_48_kDa_isoform*@Cytoplasm + HSP70*@Cytoplasm + DVL*@Cytoplasm + Actin cytoskeletal*@Cytoplasm + AXIN*@Cytoplasm + HSC70*@Cytoplasm → APC:AXIN*:Actin cytoskeletal*:DVL*:HSC70*:HSP70*:HTID1_50_48_kDa_isoform*@Cytoplasm
→ AMER1*:AXIN*:CK1_alpha_*:CK1_epsilon_*:CK1_gamma_*:DVL*|pho|pho|pho:E-Cadherin*:FZD*:GSK3*:G_alpha_o*:G_beta_*:G_gamma_*:LRP5_6*|T1479_pho|S1490_pho|T1493_pho|S1496_pho|T1530_pho|S1533_pho:PRR*:WNT*:_beta_-Arrestin2*:p120*@Endosome
→ Caspase8_sub_TRUNC_endsub_*@Cytoplasm