title: Rho GTPase Cdc42 is a direct interacting partner of Adenomatous Polyposis Coli protein and can alter its cellular localization.
abstract: 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.
authors.affiliation: Neural Stem Cell Laboratory, Institute of Medical Biology, Singapore, Singapore.
authors.forename: Thankiah
authors.initials: T
authors.lastname: Sudhaharan
authors.forename: Wah Ing
authors.initials: WI
authors.lastname: Goh
authors.forename: Kai Ping
authors.initials: KP
authors.lastname: Sem
authors.forename: Kim Buay
authors.initials: KB
authors.lastname: Lim
authors.forename: Wenyu
authors.initials: W
authors.lastname: Bu
authors.forename: Sohail
authors.initials: S
authors.lastname: Ahmed
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016466:CHO Cells; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D045325:HCT116 Cells; D006801:Humans; D011485:Protein Binding / Q000235:genetics / Q000502:physiology; D021381:Protein Transport / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution; D014162:Transfection; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology
chemical_list: C555337:APC protein, human; D025601:Adenomatous Polyposis Coli Protein; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D020764:cdc42 GTP-Binding Protein; D020741:rho GTP-Binding Proteins