NDLI: CDK1-CCNB1 creates a spindle checkpoint–permissive state by enabling MPS1 kinetochore localization

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CDK1-CCNB1 creates a spindle checkpoint–permissive state by enabling MPS1 kinetochore localization

Content Provider	Scilit
Author	Hayward, Daniel Alfonso-Pérez, Tatiana Cundell, Michael J. Hopkins, Michael Reitman-Holder, James Bancroft, James Hutter, Lukas H. Novak, Bela Barr, Francis A. Gruneberg, Ulrike
Copyright Year	2019
Description	Spindle checkpoint signaling is initiated by recruitment of the kinase MPS1 to unattached kinetochores during mitosis. We show that CDK1-CCNB1 and a counteracting phosphatase PP2A-B55 regulate the engagement of human MPS1 with unattached kinetochores by controlling the phosphorylation status of S281 in the kinetochore-binding domain. This regulation is essential for checkpoint signaling, since MPS1S281A is not recruited to unattached kinetochores and fails to support the recruitment of other checkpoint proteins. Directly tethering MPS1S281A to the kinetochore protein Mis12 bypasses this regulation and hence the requirement for S281 phosphorylation in checkpoint signaling. At the metaphase–anaphase transition, MPS1 S281 dephosphorylation is delayed because PP2A-B55 is negatively regulated by CDK1-CCNB1 and only becomes fully active once CCNB1 concentration falls below a characteristic threshold. This mechanism prolongs the checkpoint-responsive period when MPS1 can localize to kinetochores and enables a response to late-stage spindle defects. By acting together, CDK1-CCNB1 and PP2A-B55 thus create a spindle checkpoint–permissive state and ensure the fidelity of mitosis.
Related Links	https://rupress.org/jcb/article-pdf/218/4/1182/866609/jcb_201808014.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446832/pdf https://rupress.org/jcb/article-pdf/218/4/1182/1381839/jcb_201808014.pdf
Ending Page	1199
Page Count	18
Starting Page	1182
DOI	10.1083/jcb.201808014
Journal	Journal of Cell Biology
Issue Number	4
Volume Number	218
Language	English
Publisher	Rockefeller University Press
Publisher Date	2019-04-01
Access Restriction	Open
Subject Keyword	Cell Biology Pp2a Phosphorylation Proteins Checkpoint Spindle Kinetochores Mps1 B55 Kinetochore Localization Ccnb1 Journal: Journal of Cell Biology (Vol- 218, Issue- 4)
Content Type	Text
Resource Type	Article

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