Characterization of a 60S complex of the adenomatous polyposis coli tumor suppressor protein.
The tumor suppressor protein adenomatous polyposis coli (APC) is a multifunctional protein with a well characterized role in the Wnt signal transduction pathway and roles in cytoskeletal regulation and cell polarity. The soluble pool of APC protein in colon epithelial tumor cells exists in two distinct complexes fractionating at approximately 20S and approximately 60S in size. The 20S complex contains components of the beta-catenin destruction complex and probably functions in the Wnt pathway. In this study, we characterized the molecular nature of the 60S APC- containing complex by examining known potential binding partners of APC. 60S APC did not contain EB1 or diaphanous, proteins that have been reported to interact with APC and are implicated in microtubule plus end stabilization. Nor did the two other microtubule associated proteins, MAP4 or KAP3, which is thought to link APC to kinesin motor proteins, associate with the 60S complex. Minor fractions of alpha-tubulin, gamma-tubulin and IQGAP1, a Rac1 and CDC42 effector that interacts with APC, specifically associated with APC in the 60S fraction. We propose that 60S APC is a discrete high molecular weight complex with a novel function in cytoskeletal regulation in epithelial cells apart from its well established role in targeting catenin destruction or its proposed role in microtubule plus end stabilization.
Mahadevaiyer
Sreekala
S
Department of Cell Biology, University of Virginia Health Sciences Center, 1300 Jefferson Park Avenue, Charlottesville, VA 22908, USA.
Xu
Chong
C
Gumbiner
Barry M
BM
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D025601:Adenomatous Polyposis Coli Protein / Q000302:isolation & purification / Q000378:metabolism*; D002458:Cell Fractionation; D002462:Cell Membrane / Q000378:metabolism; D002852:Chromatography, Ion Exchange; D003598:Cytoskeletal Proteins / Q000378:metabolism; D045325:HCT116 Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000302:isolation & purification / Q000378:metabolism; D008970:Molecular Weight; D011485:Protein Binding; D013347:Subcellular Fractions; D014404:Tubulin / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism; D020703:ras GTPase-Activating Proteins / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D025601:Adenomatous Polyposis Coli Protein; D003598:Cytoskeletal Proteins; C101203:IQ motif containing GTPase activating protein 1; C484407:KIFAP3 protein, human; D008869:Microtubule-Associated Proteins; D014404:Tubulin; D051176:beta Catenin; D020703:ras GTPase-Activating Proteins