title: PTEN regulates PLK1 and controls chromosomal stability during cell division.
abstract: PTEN functions as a guardian of the genome through multiple mechanisms. We have previously established that PTEN maintains the structural integrity of chromosomes. In this report, we demonstrate a fundamental role of PTEN in controlling chromosome inheritance to prevent gross genomic alterations. Disruption of PTEN or depletion of PTEN protein phosphatase activity causes abnormal chromosome content, manifested by enlarged or polyploid nuclei. We further identify polo-like kinase 1 (PLK1) as a substrate of PTEN phosphatase. PTEN can physically associate with PLK1 and reduce PLK1 phosphorylation in a phosphatase-dependent manner. We show that PTEN deficiency leads to PLK1 phosphorylation and that a phospho-mimicking PLK1 mutant causes polyploidy, imitating functional deficiency of PTEN phosphatase. Inhibition of PLK1 activity or overexpression of a non-phosphorylatable PLK1 mutant reduces the polyploid cell population. These data reveal a new mechanism by which PTEN controls genomic stability during cell division.
authors.affiliation: a Department of Radiation Oncology , Weill Medical Medicine, Cornell University , New York , NY , USA.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: a Department of Radiation Oncology , Weill Medical Medicine, Cornell University , New York , NY , USA.
authors.forename: Sheng-Qi
authors.initials: SQ
authors.lastname: Hou
authors.affiliation: a Department of Radiation Oncology , Weill Medical Medicine, Cornell University , New York , NY , USA.
authors.forename: Jinxue
authors.initials: J
authors.lastname: He
authors.affiliation: a Department of Radiation Oncology , Weill Medical Medicine, Cornell University , New York , NY , USA.
authors.forename: Tingting
authors.initials: T
authors.lastname: Gu
authors.affiliation: a Department of Radiation Oncology , Weill Medical Medicine, Cornell University , New York , NY , USA.|b Present address: Institute of Systems Biomedicine, Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center , Beijing , China.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Yin
authors.affiliation: a Department of Radiation Oncology , Weill Medical Medicine, Cornell University , New York , NY , USA.
authors.forename: Wen H
authors.initials: WH
authors.lastname: Shen
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D043171:Chromosomal Instability / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D004795:Enzyme Stability / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D007621:Karyotyping; D051379:Mice; D008938:Mitosis / Q000187:drug effects; D015739:Nocodazole / Q000494:pharmacology; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011123:Polyploidy; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D008941:Spindle Apparatus / Q000187:drug effects / Q000378:metabolism; D013379:Substrate Specificity / Q000187:drug effects; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D015739:Nocodazole; D051059:PTEN Phosphohydrolase; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1; C494929:PTEN protein, human; C487757:Pten protein, mouse
keywords: Mitosis; PTEN; polo-like kinase 1; chromosome stability; phosphorylation; polyploidy