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bioRxiv · 10.1101/2020.06.22.164251

PP1 promotes cyclin B destruction and the metaphase-anaphase transition by dephosphorylating CDC20

Bancroft, J.·Holder, J.·Geraghty, Z.·Alfonso-Perez, T.·Murphy, D.·Barr, F.·Gruneberg, U.
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Abstract

Ubiquitin-dependent proteolysis of cyclin B and securin initiates sister chromatid segregation and anaphase. The anaphase promoting complex/cyclosome (APC/C) and its co-activator CDC20 form the main ubiquitin E3 ligase for these proteins. APC/CCDC20 is regulated by CDK1-cyclin B and counteracting PP1 and PP2A family phosphatases through modulation of both activating and inhibitory phosphorylations. 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 stabilises 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, but once all chromosomes have aligned rapidly degrade cyclin B and enter into anaphase in the absence of PP1 activity. PP1 therefore facilitates the metaphase-to-anaphase by promoting APC/CCDC20-dependent destruction of cyclin B in human cells.

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Bancroft, J., Holder, J., Geraghty, Z., Alfonso-Perez, T., Murphy, D., Barr, F., Gruneberg, U.. 2020-06-22. PP1 promotes cyclin B destruction and the metaphase-anaphase transition by dephosphorylating CDC20. https://doi.org/10.1101/2020.06.22.164251

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