The Gene For The APC-Binding Protein Beta-Catenin (CTNNB1) Maps To Chromosome 3p22, A Region Frequently Altered In Human Malignancies.

beta-Catenin is one of the E-cadherin associated proteins involved in the process of cellular adhesion. It has recently been shown to interact with the APC protein whose gene is known to be mutated in the germline of familial adenomatous polyposis patients. This interaction implies that beta-catenin is a potential regulator of the APC gene. The localization of the human beta-catenin gene (CTNNB1) to chromosome 3p22, by fluorescent in situ hybridization (FISH), has linked the gene to a region that is frequently altered in several human malignancies. The location of the gene and the protein interactions suggest the importance of beta-catenin in the etiology of various human cancers

APC Binds To The Novel Protein EB1.

Mutations of the APC gene play a critical role in both sporadic and familial forms of colorectal cancer. The vast majority of these mutations result in the loss of the carboxyl terminus of the protein. To further elucidate the function of APC, we searched for cellular proteins that associate with its carboxyl terminus. One million human cDNA clones were screened with the use of the interaction trap two-hybrid system, and 67 clones were found to have a phenotype suggestive of an APC-interacting protein. Nucleotide sequence analysis revealed that 48 of these clones were derived from a single novel named EBI. The association of APC and EB1 proteins was confirmed with in vitro binding assays. mAbs against EB1 were then produced and used to demonstrate the association of APC and EB1 in vivo. The EB1 gene was predicted to encode a 268-amino acid protein without significant homology to proteins with known function. However, searches of nucleotide databases did identify evidence for at least two related human genes and a yeast homologue. This conservation suggests an essential function for EB1 that might provide clues to the mechanism through which APC suppresses colonic neoplasia