Rho GTPase Cdc42 is a direct interacting partner of adenomatous polyposis coli protein and can alter its cellular localization
Sudhaharan, T. ; Goh, W.I. ; Sem, K.P. ; Lim, K.B. ; Bu, W. ; Ahmed, S.
Sudhaharan, T.
Goh, W.I.
Sem, K.P.
Bu, W.
Ahmed, S.
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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. © 2011 Sudhaharan et al.
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PLoS ONE
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Date
2011
DOI
10.1371/journal.pone.0016603
Type
Article