Aurora B regulates PP1γ–Repo-Man interactions to maintain the chromosome condensation state
Journal of Biological Chemistry(2020)
摘要
The mitotic kinase Aurora B regulates the condensation of chromatin into chromosomes by phosphorylating chromatin proteins during early mitosis, whereas the phosphatase PP1 gamma performs the opposite function. The roles of Aurora B and PP1 gamma must be tightly coordinated to maintain chromosomes at a high phosphorylation state, but the precise mechanisms regulating their function remain largely unclear. Here, mainly through immunofluorescence microscopy and co-immunoprecipitation assays, we find that dissociation of PP1 gamma from chromosomes is essential for maintaining chromosome phosphorylation. We uncover that PP1 gamma is recruited to mitotic chromosomes by its regulatory subunit Repo-Man in the absence of Aurora B activity and that Aurora B regulates dissociation of PP1 gamma by phosphorylating and disrupting PP1 gamma-Repo-Man interactions on chromatin. Overexpression of Repo-Man mutants that cannot be phosphorylated or inhibition of Aurora B kinase activity resulted in the retention of PP1 gamma on chromatin and prolonged the chromatin condensation process; a similar outcome was caused by the ectopic targeting of PP1 gamma to chromatin. Together, our findings reveal a novel regulation mechanism of chromatin condensation in which Aurora B counteracts PP1 gamma activity by releasing PP1 gamma from Repo-Man and may have important implications for understanding the regulations of dynamic structural changes of the chromosomes in mitosis.
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关键词
chromosome condensation,Aurora B,PP1γ,Repo-Man,cell cycle,chromatin,phosphoprotein phosphatase 1 (PP1),mitosis,chromatin modification
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