title: The Protein Phosphatase 2A regulatory subunit Twins stabilizes Plk4 to induce centriole amplification.
abstract: Centriole duplication is a tightly regulated process that must occur only once per cell cycle; otherwise, supernumerary centrioles can induce aneuploidy and tumorigenesis. Plk4 (Polo-like kinase 4) activity initiates centriole duplication and is regulated by ubiquitin-mediated proteolysis. Throughout interphase, Plk4 autophosphorylation triggers its degradation, thus preventing centriole amplification. However, Plk4 activity is required during mitosis for proper centriole duplication, but the mechanism stabilizing mitotic Plk4 is unknown. In this paper, we show that PP2A (Protein Phosphatase 2A(Twins)) counteracts Plk4 autophosphorylation, thus stabilizing Plk4 and promoting centriole duplication. Like Plk4, the protein level of PP2A's regulatory subunit, Twins (Tws), peaks during mitosis and is required for centriole duplication. However, untimely Tws expression stabilizes Plk4 inappropriately, inducing centriole amplification. Paradoxically, expression of tumor-promoting simian virus 40 small tumor antigen (ST), a reported PP2A inhibitor, promotes centrosome amplification by an unknown mechanism. We demonstrate that ST actually mimics Tws function in stabilizing Plk4 and inducing centriole amplification.
authors: Department of Cellular and Molecular Medicine, Arizona Cancer Center, University of Arizona, Tucson, AZ 85724, USA.
authors: Christopher W
authors: CW
authors: Brownlee
authors: Joey E
authors: JE
authors: Klebba
authors: Daniel W
authors: DW
authors: Buster
authors: Gregory C
authors: GC
authors: Rogers
mesh_terms: D000818:Animals; D002453:Cell Cycle; D002460:Cell Line; D002502:Centrioles; D004330:Drosophila; D029721:Drosophila Proteins / Q000502:physiology*; D008938:Mitosis; D010766:Phosphorylation; D054648:Protein Phosphatase 2 / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism* / Q000502:physiology*; D055550:Protein Stability; D021122:Protein Subunits
chemical_list: D029721:Drosophila Proteins; D021122:Protein Subunits; C088051:Plk4 protein, mouse; D017346:Protein Serine-Threonine Kinases; C522064:Sak protein, Drosophila; D054648:Protein Phosphatase 2