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• W2038205784 abstract "Myosin phosphatase is a heterotrimeric holoenzyme consisting of myosin phosphatase-targeting subunit 1 (MYPT1), a catalytic subunit of PP1Cβ, and a 20-kDa subunit of an unknown function. We have previously reported that myosin phosphatase also controls mitosis, apparently by antagonizing polo-like kinase 1 (PLK1). Here we found that depletion of MYPT1 by siRNA led to precocious chromatid segregation when HeLa cells were arrested at metaphase by a proteasome inhibitor, MG132, or by Cdc20 depletion. Consistently, cyclin B1 and securin were not degraded, indicating that the chromatid segregation is independent of the anaphase-promoting complex/cyclosome. Precocious segregation induced by MYPT1 depletion requires PLK1 activity because a PLK1 inhibitor, BI-2536, blocked precocious segregation. Furthermore, the expression of an unphosphorylatable mutant of SA2 (SCC3 homologue 2), a subunit of the cohesin complex, prevented precocious chromatid segregation induced by MYPT1 depletion. It has been shown that SA2 at centromeres is protected from phosphorylation by PP2A phosphatase recruited by Shugoshin (Sgo1), whereas SA2 along chromosome arms is phosphorylated by PLK1, leading to SA2 dissociation at chromosome arms. Taken together, our results suggest that hyperactivation of PLK1 caused by MYPT1 reduction could override the counteracting PP2A phosphatase, resulting in precocious chromatid segregation. We propose that SA2 at the centromeres is protected by two phosphatases. One is PP2A directly dephosphorylating SA2, and the other is myosin phosphatase counteracting PLK1." @default.
• W2038205784 created "2016-06-24" @default.
• W2038205784 creator A5001795579 @default.
• W2038205784 creator A5020332354 @default.
• W2038205784 creator A5031346152 @default.
• W2038205784 date "2011-03-01" @default.
• W2038205784 modified "2023-10-17" @default.
• W2038205784 title "Myosin Phosphatase-targeting Subunit 1 Controls Chromatid Segregation" @default.
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• W2038205784 doi "https://doi.org/10.1074/jbc.m110.169722" @default.
• W2038205784 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3060533" @default.
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• W2038205784 hasPublicationYear "2011" @default.
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