The APC gene product associates with microtubules in vivo and promotes their assembly in vitro

Abstract

Defects in the APC gene occur frequently in patients with familial adenomatous polyposis coli and are associated with the progression of sporadic tumors of the colon and stomach. We examined the subcellular location of adenomatous polyposis coli (APC) protein resulting from transient expression of full length and partial APC complementary DNAs in epithelial cells. Immunofluorescent detection revealed an association of APC with cytoplasmic microtubules. Expression of partial complementary DNA constructs indicated that the carboxy-terminal region of the APC protein, typically deleted in cancers, is essential for this association. The same APC polypeptides that associated with microtubules in vivo also dramatically promoted their assembly in vitro. These results suggest that wild-type APC protein binds to and affects the assembly of microtubules, whereas the mutants identified in tumors have lost this activity.