4.6 Article

Ki67 Antigen Contributes to the Timely Accumulation of Protein Phosphatase 1γ on Anaphase Chromosomes

期刊

JOURNAL OF BIOLOGICAL CHEMISTRY
卷 289, 期 33, 页码 22877-22887

出版社

AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M114.556647

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资金

  1. RIKEN Special Project Funding for Basic Science in Cellular System Project Research
  2. Japan Society for the Promotion of Science KAKENHI [24657124]
  3. RIKEN Incentive Research Fund
  4. Grants-in-Aid for Scientific Research [26650070, 24657124] Funding Source: KAKEN

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Ki67 is a protein widely used as cell-proliferation marker, with its cellular functions being hardly unveiled. In this paper, we present the direct interaction between Ki67 and PP1 gamma, a protein phosphatase showing characteristic accumulation on anaphase chromosomes via the canonical PP1-binding motif within Ki67. In cells depleted of Ki67, PP1 gamma is targeted to anaphase chromosomes less efficiently. Additionally, overexpression of Ki67, but not a mutant form without the ability to bind PP1 gamma, induced ectopic localization of PP1 gamma on metaphase chromosomes. These observations demonstrate that Ki67 is one factor that defines the cellular behavior of PP1 gamma in anaphase. To explore the specific roles of the subset of PP1 gamma recruited on chromosome via its interaction with Ki67 (PP1 gamma-Ki67), endogenous Ki67 was replaced with a Ki67 mutant deficient in its ability to interact with PP1 gamma. Although no obvious defects in the progression of mitosis were observed, the timing of dephosphorylation of the mutant Ki67 in anaphase was delayed, indicating that Ki67 itself is one of the substrates of PP1 gamma -Ki67.

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