Rho GTPase Cdc42 is a direct interacting partner of Adenomatous Polyposis Coli protein and can alter its cellular localization.

• Main Authors: Thankiah Sudhaharan, Wah Ing Goh, Kai Ping Sem, Kim Buay Lim, Wenyu Bu, Sohail Ahmed
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2011-01-01
• Series: PLoS ONE
• Online Access: http://europepmc.org/articles/PMC3032772?pdf=render

Adenomatous Polyposis Coli (APC) is a tumor suppressor gene product involved in colon cancer. APC is a large multidomain molecule of 2843 amino acid residues and connects cell-cell adhesion, the F-actin/microtubule cytoskeleton and the nucleus. Here we show that Cdc42 interacts directly with the first three armadillo repeats of APC by yeast two-hybrid screens. We confirm the Cdc42-APC interaction using pulldown assays in vitro and FRET assays in vivo. Interestingly, Cdc42 interacts with APC at leading edge sites where F-actin is enriched. In contrast, Cdc42 interacts with the truncated mutant APC¹⁻¹⁶³⁸ in cellular puncta associated with the golgi-lysozome pathway in transfected CHO cells. In HCT116 and SW480 cells, Cdc42 induces the relocalization of endogenous APC and the mutant APC¹⁻¹³³⁸ to the plasma membrane and cellular puncta, respectively. Taken together, these data indicate that the Cdc42-APC interaction induces localization of both APC and mutant APC and may thus play a direct role in the functions of these proteins.