Adenomatous polyposis coli (APC) plays multiple roles in the intestinal and colorectal epithelia.
The adenomatous polyposis coli (APC) gene is mutated in familial adenomatous polyposis and in most sporadic colorectal tumors. During both embryonic and postnatal periods, APC is widely expressed in a variety of tissues, including the brain and gastrointestinal tract. The APC gene product (APC) is a large multidomain protein consisting of 2843 amino acids. APC downregulates the Wnt signaling pathway through its binding to beta-catenin and Axin. Most mutated APC proteins in colorectal tumors lack the beta-catenin-binding regions and fail to inhibit Wnt signaling, leading to the overproliferation of tumor cells. Several mouse models (APC580D, APCDelta716, APC1309, APCMin, APC1638T) have been established to investigate carcinogenesis caused by APC mutations. APC also binds to APC-stimulated guanine nucleotide exchange factor, the kinesin superfamily-associated protein 3, IQGAP1, microtubules, EB1, and discs large (DLG). APC has both nuclear localization signals and nuclear export signals in its molecule, suggesting its occasional nuclear localization and export of beta-catenin from the nucleus. APC is highly expressed in the intestinal and colorectal epithelia and may be involved in homeostasis of the enterocyte renewal phenomena, in which proliferation, migration, differentiation, and apoptosis are highly regulated both temporally and spatially. Through the many binding proteins mentioned, APC can exert multiple functions involved in epithelial homeostasis.
Senda
Takao
T
Department of Anatomy I, Fujita Health University School of Medicine, Toyoake, Aichi, 470-1192, Japan. tsenda@fujita-hu.ac.jp
Iizuka-Kogo
Akiko
A
Onouchi
Takanori
T
Shimomura
Atsushi
A
D025601:Adenomatous Polyposis Coli Protein / Q000172:deficiency / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D003106:Colon / Q000502:physiology / Q000503:physiopathology*; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D004848:Epithelium / Q000502:physiology / Q000503:physiopathology; D015972:Gene Expression Regulation, Neoplastic; D017491:Genes, APC; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008870:Microtubules / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D051381:Rats; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction
D025601:Adenomatous Polyposis Coli Protein; D012097:Repressor Proteins