THE APC GENE-PRODUCT ASSOCIATES WITH MICROTUBULES IN-VIVO AND PROMOTES THEIR ASSEMBLY IN-VITRO

Defects in the APC gene occur frequently in patients with familial ade nomatous polyposis coli and are associated with the progression of spo radic tumors of the colon and stomach. We examined the subcellular loc ation of adenomatous polyposis coli (APC) protein resulting from trans ient expression of full length and partial APC complementary DNAs in e pithelial cells. Immunofluorescent detection revealed an association o f APC with cytoplasmic microtubules. Expression of partial complementa ry DNA constructs indicated that the carboxy-terminal region of the AP C protein, typically deleted in cancers, is essential for this associa tion. The same APC polypeptides that associated with microtubules in v ivo also dramatically promoted their assembly in vitro. These results suggest that wild-type APC protein binds to and affects the assembly o f microtubules, whereas the mutants identified in tumors have lost thi s activity.