Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 291, Issue 40, Pages 21123-+Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M116.745372
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Funding
- Chinese Natural Science Foundation [31430054, 31320103904, 91313303, 31621002, 31501095, 31671405, 31371363, 31601097]
- Chinese 973 Project [2012CB917204, 2012CB945002, 2002CB713700]
- Anhui Province Key Project Grant [08040102005]
- Chinese Academy of Sciences Center of Excellence Grant [2015HSC-UE010]
- Anhui Provincial Natural Science Foundation [1508085SMC213]
- National Institutes of Health [DK056292, CA164133]
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During cell division, accurate chromosome segregation is tightly regulated by Polo-like kinase 1 (PLK1) and opposing activities of Aurora B kinase and protein phosphatase 1 (PP1). However, the regulatory mechanisms underlying the aforementioned hierarchical signaling cascade during mitotic chromosome segregation have remained elusive. Sds22 is a conserved regulator of PP1 activity, but how it regulates PP1 activity in space and time during mitosis remains elusive. Here we show that Sds22 is a novel and cognate substrate of PLK1 in mitosis, and the phosphorylation of Sds22 by PLK1 elicited an inhibition of PP1-mediated dephosphorylation of Aurora B at threonine 232 (Thr(232)) in a dose-dependent manner. Overexpression of a phosphomimetic mutant of Sds22 causes a dramatic increase in mitotic delay, whereas overexpression of a non-phosphorylatable mutant of Sds22 results in mitotic arrest. Mechanistically, the phosphorylation of Sds22 by PLK1 strengthens the binding of Sds22 to PP1 and inhibits the dephosphorylation of Thr(232) of Aurora B to ensure arobust, error-freemetaphase-anaphasetransition. Thesefindings delineate a conserved signaling hierarchy that orchestrates dynamic protein phosphorylation and dephosphorylation of critical mitotic regulators during chromosome segregation to guard chromosome stability.
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