Bancroft, J; Holder, J; Geraghty, Z; Alfonso-Pérez, T; Murphy, D; Barr, FA; Gruneberg, U
(2020)
PP1 promotes cyclin B destruction and the metaphase–anaphase transition by dephosphorylating CDC20.
Molecular Biology of the Cell, 31 (21).
pp. 2315-2330.
ISSN 1059-1524
https://doi.org/10.1091/mbc.e20-04-0252
SGUL Authors: Murphy, Daniel Aodhan James
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Abstract
Ubiquitin-dependent proteolysis of cyclin B and securin initiates sister chromatid segregation and anaphase. The anaphase-promoting complex/cyclosome and its coactivator CDC20 (APC/CCDC20) form the main ubiquitin E3 ligase for these two proteins. APC/CCDC20 is regulated by CDK1-cyclin B and counteracting PP1 and PP2A family phosphatases through modulation of both activating and inhibitory phosphorylation. Here, we report that PP1 promotes cyclin B destruction at the onset of anaphase by removing specific inhibitory phosphorylation in the N-terminus of CDC20. Depletion or chemical inhibition of PP1 stabilizes cyclin B and results in a pronounced delay at the metaphase-to-anaphase transition after chromosome alignment. This requirement for PP1 is lost in cells expressing CDK1 phosphorylation–defective CDC206A mutants. These CDC206A cells show a normal spindle checkpoint response and rapidly destroy cyclin B once all chromosomes have aligned and enter into anaphase in the absence of PP1 activity. PP1 therefore facilitates the metaphase-to-anaphase transition by promoting APC/CCDC20-dependent destruction of cyclin B in human cells.
Item Type: | Article | ||||||||||||
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Additional Information: | © 2020 Bancroft, Holder, Geraghty, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). | ||||||||||||
Keywords: | 06 Biological Sciences, 11 Medical and Health Sciences, Developmental Biology | ||||||||||||
SGUL Research Institute / Research Centre: | Academic Structure > Institute of Medical & Biomedical Education (IMBE) | ||||||||||||
Journal or Publication Title: | Molecular Biology of the Cell | ||||||||||||
ISSN: | 1059-1524 | ||||||||||||
Language: | en | ||||||||||||
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Publisher License: | Creative Commons: Attribution-Noncommercial-Share Alike 3.0 | ||||||||||||
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URI: | https://openaccess.sgul.ac.uk/id/eprint/114310 | ||||||||||||
Publisher's version: | https://doi.org/10.1091/mbc.e20-04-0252 |
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