NUCLEAR FUNCTIONS OF ADENOMATOUS POLYPOSIS COLI: REGULATION OF THE G2-M CELL CYCLE TRANSITION & INTERMEDIATE FILAMENT INTERACTION

Abstract

Mutations in Adenomatous Polyposis Coli (APC) initiate most colorectal cancers. APC is implicated in regulating cell cycle and the cytoskeleton. I identified topoisomerase IIalpha (topo IIalpha), a regulator of G2 decatenation checkpoint, in complex with APC. Topo IIalpha interacts with two separate domains in the middle of APC, M2- and M3-APC. Expression of either domain resulted in G2 cell cycle arrest, likely a response to inhibition of topo IIalpha activity. However, the G2 arrest only occurred in cells containing normal levels of topo IIalpha. In a related study, I characterized a new APC antibody we generated and purified. Using this novel reagent to immunoprecipitate APC protein, I identified 42 potential APC binding proteins. Among these, intermediate filament protein lamin B1 was verified to interact with APC in both cultured cells and human tissue. Together, I provide evidence supporting a role for APC in G2-M cell cycle transition and in cytoskeletal regulation.