THE ADENOMATOUS POLYPOSIS-COLI (APC) TUMOR-SUPPRESSOR

Defects in the APC gene are inarguably linked to the progression of co lon cancers that arise both sporadically and through the transmission of germline mutations. Genetic evidence from humans and mouse models s uggest that APC is a classic tumor suppressor in that both alleles lik ely require inactivation for tumor growth to ensue, Nearly all of the mutations, germline and somatic, result in premature termination of:he single polypeptide chain, normally consisting of 2843 amino acids. Se veral definable motifs have now been mapped to the linear amino acid s equence of the APC polypeptide. These include an oligomerization domai n, armadillo repeats, binding sites for beta-catenin, the human discs large protein, microtubules, and other proteins of unknown function. I nactivation of APC in cancer is likely due to loss of function(s) norm ally associated with the deleted protein structure.