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Gene Review

APC  -  adenomatous polyposis coli

Homo sapiens

Synonyms: Adenomatous polyposis coli protein, BTPS2, DP2, DP2.5, DP3, ...
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Disease relevance of APC


Psychiatry related information on APC

  • The LOH rate was measured at the BRCA1/2 loci and compared with that at a control locus (APC) using free DNA from the ductal lavage fluid of BRCA carriers and predictive test negative controls [5].
  • The aim of this study is to assess the utility of the APC mutation screening compared to the degree of the rectal polyposis in surgical decision making [6].
  • Depletion of Cdh1 stabilizes Id proteins in neurons, whereas Id2 D-box mutants are impaired for Cdh1 binding and remain stable in cells that exit from the cell cycle and contain active APC/C(Cdh1) [7].
  • MHC multimerization, antigen expression and the induction of APC amnesia in the developing immune response [8].
  • The premature suspension of the Alzheimer Disease Anti-inflammatory Prevention (ADAPT) and the Adenoma Prevention with Celecoxib (APC) trials prompted intense review of the cardiovascular safety profile of selective and nonselective cyclooxygenase (COX) inhibitors [9].

High impact information on APC

  • It appears therefore that the SAP/SH2D1A gene controls signaling via the SLAM family of surface receptors and thus may play a fundamental role in T cell and APC interactions during viral infections [10].
  • The macrophage, being the most ubiquitous cell and the one capable of interacting with many proteins, is our candidate as the major APC involved in the recruitment and enlargement of clones T cells [11].
  • The observations that macrophages can release proteins partially altered implies that there may be cooperativity among the various APC [11].
  • On the basis of the studies discussed in the first section, it appears that the recruitment of most helper-T cell clones takes place by APC that can internalize and process the protein antigens, be they soluble or part of the structure of microorganisms [11].
  • Ablation of Evi5 induces precocious degradation of Emi1 by the Plk/SCF(betaTrCP) pathway, causing premature APC/C activation; cyclin destruction; cell-cycle arrest; centrosome overduplication; and, finally, mitotic catastrophe [12].

Chemical compound and disease context of APC


Biological context of APC


Anatomical context of APC


Associations of APC with chemical compounds

  • The kinase was highly active toward APC in vitro and promoted a sodium dodecyl sulfate gel band shift that was also evident for endogenous APC from cells expressing the mutant beta-catenin [25].
  • Recent studies have implicated APC in controlling retinoic acid biosynthesis during normal intestinal development through a WNT-independent mechanism [14].
  • In contrast, mutations in the NH2-terminal regulatory domain of beta-catenin (CTNNB1) were found in 13 of 27 (48%) CR tumors lacking APC mutations [26].
  • Furthermore, we have shown that APC mutation-mediated resistance to apoptosis can be overcome by cotreatment with Flavopiridol, which promotes survivin degradation [27].
  • These results point to a role for beta-catenin ubiquitination, proteasomal degradation, and potentially a serine kinase other than glycogen synthase kinase-3beta in the tumor-suppressive actions of APC [13].

Physical interactions of APC

  • Consistent with this hypothesis, membrane-tethered beta-catenin coimmunoprecipitates with APC and relocalizes APC to the membrane in cells [28].
  • The expression and assembly of the E-cadherin/catenin complex does not appear to be affected by the presence of APC and or beta-CATENIN mutations [29].
  • The RGS domain directly interacted with the region containing the 20-amino acid repeats but not with that containing the 15-amino acid repeats of APC, although both regions are known to bind to beta-catenin [30].
  • The canonical pathway is induced by the Axin/adenomatous polyposis coli (APC)/glycogen synthase kinase-3beta (GSK-3beta) complex which is dependent on GSK-3beta phosphorylation [31].
  • RP1, a new member of the adenomatous polyposis coli-binding EB1-like gene family, is differentially expressed in activated T cells [32].
  • APC formed a complex with Bcl-2 in mitochondrial fractions, and this may contribute to the APC-dependent regulation of Bcl-2 [33].

Enzymatic interactions of APC

  • Differences between the interaction of beta-catenin with non-phosphorylated and single-mimicked phosphorylated 20-amino acid residue repeats of the APC protein [34].
  • In a reconstituted system, TPX2 is efficiently ubiquitinated by APC/C that has been activated by Cdh1 [35].
  • Bub1 is ubiquitinated by immunopurified APC/C(Cdh1) in vitro [36].
  • Aurora B is efficiently ubiquitinated in an in vitro reconstituted system by APC/C that had been activated by Cdh1 [37].
  • Western blotting using a monoclonal antibody that recognizes an epitope between amino acid residues 307 and 506 of human FV showed that FV was completely cleaved by APC at the beginning of the rhFVIII inactivation process [38].

Co-localisations of APC


Regulatory relationships of APC


Other interactions of APC

  • Loss of functional APC protein results in the accumulation of beta-catenin [3].
  • Normally, cytoplasmic beta-catenin associates with APC and axin and is continuously phosphorylated by GSK-3beta, marking it for proteasomal degradation [47].
  • Nuclear and cytoplasmic immunoreactivity for the MYH protein were observed in normal colorectal mucosa, in sporadic colorectal carcinomas, and in adenomas and carcinomas from patients carrying APC germline mutations [48].
  • We investigated the mechanism for AFAP in patients carrying a mutant APC allele (APC(AS9)) that has a mutation in the alternatively spliced region of exon 9 [49].
  • APC mutation rates in the msh2 strain (2.4 x 10-6) and the mlh1 strain (1.7 x 10-6) were also significantly, but less dramatically, elevated over background [50].
  • Hypermethylation of APC concurrently with either MGMT or hMLH1 was strongly associated with occurrence of G-to-A transitions in APC [odds ratio (OR), 26.8; P < 0.0002 from multivariable logic regression model], but C-to-T transitions had no associations [51].

Analytical, diagnostic and therapeutic context of APC


  1. The molecular basis of Turcot's syndrome. Hamilton, S.R., Liu, B., Parsons, R.E., Papadopoulos, N., Jen, J., Powell, S.M., Krush, A.J., Berk, T., Cohen, Z., Tetu, B. N. Engl. J. Med. (1995) [Pubmed]
  2. Indian Hedgehog is an antagonist of Wnt signaling in colonic epithelial cell differentiation. van den Brink, G.R., Bleuming, S.A., Hardwick, J.C., Schepman, B.L., Offerhaus, G.J., Keller, J.J., Nielsen, C., Gaffield, W., van Deventer, S.J., Roberts, D.J., Peppelenbosch, M.P. Nat. Genet. (2004) [Pubmed]
  3. Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells. Tetsu, O., McCormick, F. Nature (1999) [Pubmed]
  4. Caspase cleavage of the APC tumor suppressor and release of an amino-terminal domain is required for the transcription-independent function of APC in apoptosis. Qian, J., Steigerwald, K., Combs, K.A., Barton, M.C., Groden, J. Oncogene (2007) [Pubmed]
  5. Loss of heterozygosity at the BRCA1 and BRCA2 loci detected in ductal lavage fluid from BRCA gene mutation carriers and controls. Locke, I., Kote-Jarai, Z., Bancroft, E., Bullock, S., Jugurnauth, S., Osin, P., Nerurkar, A., Izatt, L., Pichert, G., Gui, G.P., Eeles, R.A. Cancer Epidemiol. Biomarkers Prev. (2006) [Pubmed]
  6. Balance between endoscopic and genetic information in the choice of ileorectal anastomosis for familial adenomatous polyposis. Valanzano, R., Ficari, F., Curia, M.C., Aceto, G., Veschi, S., Cama, A., Battista, P., Tonelli, F. Journal of surgical oncology (2007) [Pubmed]
  7. Degradation of Id2 by the anaphase-promoting complex couples cell cycle exit and axonal growth. Lasorella, A., Stegmüller, J., Guardavaccaro, D., Liu, G., Carro, M.S., Rothschild, G., de la Torre-Ubieta, L., Pagano, M., Bonni, A., Iavarone, A. Nature (2006) [Pubmed]
  8. MHC multimerization, antigen expression and the induction of APC amnesia in the developing immune response. Lake, R.A., Robinson, B.W., Hayball, J.D. Immunol. Cell Biol. (1999) [Pubmed]
  9. The cardiovascular toxicity of selective and nonselective cyclooxygenase inhibitors: comparisons, contrasts, and aspirin confounding. Konstantinopoulos, P.A., Lehmann, D.F. Journal of clinical pharmacology. (2005) [Pubmed]
  10. X-linked lymphoproliferative disease: a progressive immunodeficiency. Morra, M., Howie, D., Grande, M.S., Sayos, J., Wang, N., Wu, C., Engel, P., Terhorst, C. Annu. Rev. Immunol. (2001) [Pubmed]
  11. Antigen-presenting function of the macrophage. Unanue, E.R. Annu. Rev. Immunol. (1984) [Pubmed]
  12. The evi5 oncogene regulates cyclin accumulation by stabilizing the anaphase-promoting complex inhibitor emi1. Eldridge, A.G., Loktev, A.V., Hansen, D.V., Verschuren, E.W., Reimann, J.D., Jackson, P.K. Cell (2006) [Pubmed]
  13. The ubiquitin-proteasome pathway and serine kinase activity modulate adenomatous polyposis coli protein-mediated regulation of beta-catenin-lymphocyte enhancer-binding factor signaling. Easwaran, V., Song, V., Polakis, P., Byers, S. J. Biol. Chem. (1999) [Pubmed]
  14. Up-regulation of CYP26A1 in adenomatous polyposis coli-deficient vertebrates via a WNT-dependent mechanism: implications for intestinal cell differentiation and colon tumor development. Shelton, D.N., Sandoval, I.T., Eisinger, A., Chidester, S., Ratnayake, A., Ireland, C.M., Jones, D.A. Cancer Res. (2006) [Pubmed]
  15. Molecular analysis of sulindac-resistant adenomas in familial adenomatous polyposis. Keller, J.J., Offerhaus, G.J., Drillenburg, P., Caspers, E., Musler, A., Ristimäki, A., Giardiello, F.M. Clin. Cancer Res. (2001) [Pubmed]
  16. Nitric oxide synthase 2 mRNA expression in relation to p53 and adenomatous polyposis coli mutations in primary colorectal adenocarcinomas. Fransén, K., Dimberg, J., Osterström, A., Olsson, A., Söderkvist, P., Sirsjö, A. Surgery (2002) [Pubmed]
  17. Progression of familial adenomatous polyposis (FAP) colonic cells after transfer of the src or polyoma middle T oncogenes: cooperation between src and HGF/Met in invasion. Empereur, S., Djelloul, S., Di Gioia, Y., Bruyneel, E., Mareel, M., Van Hengel, J., Van Roy, F., Comoglio, P., Courtneidge, S., Paraskeva, C., Chastre, E., Gespach, C. Br. J. Cancer (1997) [Pubmed]
  18. Identification and characterization of the familial adenomatous polyposis coli gene. Groden, J., Thliveris, A., Samowitz, W., Carlson, M., Gelbert, L., Albertsen, H., Joslyn, G., Stevens, J., Spirio, L., Robertson, M. Cell (1991) [Pubmed]
  19. Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Morin, P.J., Sparks, A.B., Korinek, V., Barker, N., Clevers, H., Vogelstein, B., Kinzler, K.W. Science (1997) [Pubmed]
  20. Crystal structure of a beta-catenin/axin complex suggests a mechanism for the beta-catenin destruction complex. Xing, Y., Clements, W.K., Kimelman, D., Xu, W. Genes Dev. (2003) [Pubmed]
  21. Concordance of genetic alterations in poorly differentiated colorectal neuroendocrine carcinomas and associated adenocarcinomas. Vortmeyer, A.O., Lubensky, I.A., Merino, M.J., Wang, C.Y., Pham, T., Furth, E.E., Zhuang, Z. J. Natl. Cancer Inst. (1997) [Pubmed]
  22. Identification of a link between the tumour suppressor APC and the kinesin superfamily. Jimbo, T., Kawasaki, Y., Koyama, R., Sato, R., Takada, S., Haraguchi, K., Akiyama, T. Nat. Cell Biol. (2002) [Pubmed]
  23. A role for the Adenomatous Polyposis Coli protein in chromosome segregation. Kaplan, K.B., Burds, A.A., Swedlow, J.R., Bekir, S.S., Sorger, P.K., Näthke, I.S. Nat. Cell Biol. (2001) [Pubmed]
  24. The APC tumor suppressor controls entry into S-phase through its ability to regulate the cyclin D/RB pathway. Heinen, C.D., Goss, K.H., Cornelius, J.R., Babcock, G.F., Knudsen, E.S., Kowalik, T., Groden, J. Gastroenterology (2002) [Pubmed]
  25. Deletion of an amino-terminal sequence beta-catenin in vivo and promotes hyperphosporylation of the adenomatous polyposis coli tumor suppressor protein. Munemitsu, S., Albert, I., Rubinfeld, B., Polakis, P. Mol. Cell. Biol. (1996) [Pubmed]
  26. Mutational analysis of the APC/beta-catenin/Tcf pathway in colorectal cancer. Sparks, A.B., Morin, P.J., Vogelstein, B., Kinzler, K.W. Cancer Res. (1998) [Pubmed]
  27. Adenomatous polyposis coli determines sensitivity to histone deacetylase inhibitor-induced apoptosis in colon cancer cells. Huang, X., Guo, B. Cancer Res. (2006) [Pubmed]
  28. Analysis of the signaling activities of localization mutants of beta-catenin during axis specification in Xenopus. Miller, J.R., Moon, R.T. J. Cell Biol. (1997) [Pubmed]
  29. Characterization of the E-cadherin/catenin complex in colorectal carcinoma cell lines. El-Bahrawy, M., Poulsom, R., Rowan, A.J., Tomlinson, I.T., Alison, M.R., Poulsom, S.R., Tomlinson, I.T. International journal of experimental pathology. (2004) [Pubmed]
  30. Axin, a negative regulator of the wnt signaling pathway, directly interacts with adenomatous polyposis coli and regulates the stabilization of beta-catenin. Kishida, S., Yamamoto, H., Ikeda, S., Kishida, M., Sakamoto, I., Koyama, S., Kikuchi, A. J. Biol. Chem. (1998) [Pubmed]
  31. IKKalpha stabilizes cytosolic beta-catenin by inhibiting both canonical and non-canonical degradation pathways. Carayol, N., Wang, C.Y. Cell. Signal. (2006) [Pubmed]
  32. RP1, a new member of the adenomatous polyposis coli-binding EB1-like gene family, is differentially expressed in activated T cells. Renner, C., Pfitzenmeier, J.P., Gerlach, K., Held, G., Ohnesorge, S., Sahin, U., Bauer, S., Pfreundschuh, M. J. Immunol. (1997) [Pubmed]
  33. Mitochondrial targeting of adenomatous polyposis coli protein is stimulated by truncating cancer mutations: regulation of Bcl-2 and implications for cell survival. Brocardo, M., Lei, Y., Tighe, A., Taylor, S.S., Mok, M.T., Henderson, B.R. J. Biol. Chem. (2008) [Pubmed]
  34. Differences between the interaction of beta-catenin with non-phosphorylated and single-mimicked phosphorylated 20-amino acid residue repeats of the APC protein. Tickenbrock, L., Kössmeier, K., Rehmann, H., Herrmann, C., Müller, O. J. Mol. Biol. (2003) [Pubmed]
  35. Anaphase-promoting complex/cyclosome controls the stability of TPX2 during mitotic exit. Stewart, S., Fang, G. Mol. Cell. Biol. (2005) [Pubmed]
  36. KEN-Box-dependent Degradation of the Bub1 Spindle Checkpoint Kinase by the Anaphase-promoting Complex/Cyclosome. Qi, W., Yu, H. J. Biol. Chem. (2007) [Pubmed]
  37. Destruction box-dependent degradation of aurora B is mediated by the anaphase-promoting complex/cyclosome and Cdh1. Stewart, S., Fang, G. Cancer Res. (2005) [Pubmed]
  38. Comparison of activated protein C/protein S-mediated inactivation of human factor VIII and factor V. Lu, D., Kalafatis, M., Mann, K.G., Long, G.L. Blood (1996) [Pubmed]
  39. Nuclear accumulation of full-length and truncated adenomatous polyposis coli protein in tumor cells depends on proliferation. Fagman, H., Larsson, F., Arvidsson, Y., Meuller, J., Nordling, M., Martinsson, T., Helmbrecht, K., Brabant, G., Nilsson, M. Oncogene (2003) [Pubmed]
  40. The dynamic behavior of the APC-binding protein EB1 on the distal ends of microtubules. Mimori-Kiyosue, Y., Shiina, N., Tsukita, S. Curr. Biol. (2000) [Pubmed]
  41. NKG2D-mediated cytotoxicity toward oligodendrocytes suggests a mechanism for tissue injury in multiple sclerosis. Saikali, P., Antel, J.P., Newcombe, J., Chen, Z., Freedman, M., Blain, M., Cayrol, R., Prat, A., Hall, J.A., Arbour, N. J. Neurosci. (2007) [Pubmed]
  42. Adenomatous polyposis coli is down-regulated by the ubiquitin-proteasome pathway in a process facilitated by Axin. Choi, J., Park, S.Y., Costantini, F., Jho, E.H., Joo, C.K. J. Biol. Chem. (2004) [Pubmed]
  43. The adenomatous polyposis coli tumor suppressor gene regulates expression of cyclooxygenase-2 by a mechanism that involves retinoic acid. Eisinger, A.L., Nadauld, L.D., Shelton, D.N., Peterson, P.W., Phelps, R.A., Chidester, S., Stafforini, D.M., Prescott, S.M., Jones, D.A. J. Biol. Chem. (2006) [Pubmed]
  44. Mutations in APC, CTNNB1 and K-ras genes and expression of hMLH1 in sporadic colorectal carcinomas from the Netherlands Cohort Study. Lüchtenborg, M., Weijenberg, M.P., Wark, P.A., Saritas, A.M., Roemen, G.M., van Muijen, G.N., de Bruïne, A.P., van den Brandt, P.A., de Goeij, A.F. BMC Cancer (2005) [Pubmed]
  45. Gut-enriched Krüppel-like factor regulates colonic cell growth through APC/beta-catenin pathway. Stone, C.D., Chen, Z.Y., Tseng, C.C. FEBS Lett. (2002) [Pubmed]
  46. APC 3 x 15 beta-catenin-binding domain potentiates beta-catenin association to TBP and upregulates TCF-4 transcriptional activity. Roura, S., Martínez, D., Piedra, J., Miravet, S., García de Herreros, A., Duñach, M. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  47. Axin-mediated CKI phosphorylation of beta-catenin at Ser 45: a molecular switch for the Wnt pathway. Amit, S., Hatzubai, A., Birman, Y., Andersen, J.S., Ben-Shushan, E., Mann, M., Ben-Neriah, Y., Alkalay, I. Genes Dev. (2002) [Pubmed]
  48. Immunohistochemical expression of MYH protein can be used to identify patients with MYH-associated polyposis. Di Gregorio, C., Frattini, M., Maffei, S., Ponti, G., Losi, L., Pedroni, M., Venesio, T., Bertario, L., Varesco, L., Risio, M., Ponz de Leon, M. Gastroenterology (2006) [Pubmed]
  49. Inactivation of germline mutant APC alleles by attenuated somatic mutations: a molecular genetic mechanism for attenuated familial adenomatous polyposis. Su, L.K., Barnes, C.J., Yao, W., Qi, Y., Lynch, P.M., Steinbach, G. Am. J. Hum. Genet. (2000) [Pubmed]
  50. A functional assay for mutations in tumor suppressor genes caused by mismatch repair deficiency. Ji, H.P., King, M.C. Hum. Mol. Genet. (2001) [Pubmed]
  51. Epigenetic-genetic interactions in the APC/WNT, RAS/RAF, and P53 pathways in colorectal carcinoma. Suehiro, Y., Wong, C.W., Chirieac, L.R., Kondo, Y., Shen, L., Webb, C.R., Chan, Y.W., Chan, A.S., Chan, T.L., Wu, T.T., Rashid, A., Hamanaka, Y., Hinoda, Y., Shannon, R.L., Wang, X., Morris, J., Issa, J.P., Yuen, S.T., Leung, S.Y., Hamilton, S.R. Clin. Cancer Res. (2008) [Pubmed]
  52. Apical membrane localization of the adenomatous polyposis coli tumor suppressor protein and subcellular distribution of the beta-catenin destruction complex in polarized epithelial cells. Reinacher-Schick, A., Gumbiner, B.M. J. Cell Biol. (2001) [Pubmed]
  53. Role of the adenomatous polyposis coli gene product in human cardiac development and disease. Rezvani, M., Liew, C.C. J. Biol. Chem. (2000) [Pubmed]
  54. Increased beta-catenin protein and somatic APC mutations in sporadic aggressive fibromatoses (desmoid tumors). Alman, B.A., Li, C., Pajerski, M.E., Diaz-Cano, S., Wolfe, H.J. Am. J. Pathol. (1997) [Pubmed]
  55. Adenomatous polyposis coli gene mutation alters proliferation through its beta-catenin-regulatory function in aggressive fibromatosis (desmoid tumor). Li, C., Bapat, B., Alman, B.A. Am. J. Pathol. (1998) [Pubmed]
  56. Optimal use of a panel of methylation markers with GSTP1 hypermethylation in the diagnosis of prostate adenocarcinoma. Tokumaru, Y., Harden, S.V., Sun, D.I., Yamashita, K., Epstein, J.I., Sidransky, D. Clin. Cancer Res. (2004) [Pubmed]
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