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Fcp1-dependent dephosphorylation is required for M-phase-promoting factor inactivation at mitosis exit

Correct execution of mitosis in eukaryotes relies on timely activation and inactivation of cyclin B-dependent kinase 1 (cdk1), the M-phase-promoting factor (MPF). Once activated, MPF is sustained until mitotic spindle assembly by phosphorylation-dependent feedback loops that prevent inhibitory phosp...

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Autores principales: Visconti, Roberta, Palazzo, Luca, Della Monica, Rosa, Grieco, Domenico
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Pub. Group 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3621406/
https://www.ncbi.nlm.nih.gov/pubmed/22692537
http://dx.doi.org/10.1038/ncomms1886
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author Visconti, Roberta
Palazzo, Luca
Della Monica, Rosa
Grieco, Domenico
author_facet Visconti, Roberta
Palazzo, Luca
Della Monica, Rosa
Grieco, Domenico
author_sort Visconti, Roberta
collection PubMed
description Correct execution of mitosis in eukaryotes relies on timely activation and inactivation of cyclin B-dependent kinase 1 (cdk1), the M-phase-promoting factor (MPF). Once activated, MPF is sustained until mitotic spindle assembly by phosphorylation-dependent feedback loops that prevent inhibitory phosphorylation of cdk1 and ubiquitin-dependent degradation of cyclin B. Whether subsequent MPF inactivation and anaphase onset require a specific phosphatase(s) to reverse these feedback loops is not known. Here we show through biochemical and genetic evidence that timely MPF inactivation requires activity of the essential RNA polymerase II-carboxy-terminal domain phosphatase Fcp1, in a transcription-independent manner. We identify Cdc20, a coactivator of the ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C) required for cyclin degradation and anaphase onset, USP44, a deubiquitinating peptidase that opposes APC/C action, and Wee1, a cdk1 inhibitory kinase, as relevant Fcp1 targets. We propose that Fcp1 has a crucial role in the liaison between dephosphorylation and ubiquitination that drives mitosis exit.
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spelling pubmed-36214062013-04-10 Fcp1-dependent dephosphorylation is required for M-phase-promoting factor inactivation at mitosis exit Visconti, Roberta Palazzo, Luca Della Monica, Rosa Grieco, Domenico Nat Commun Article Correct execution of mitosis in eukaryotes relies on timely activation and inactivation of cyclin B-dependent kinase 1 (cdk1), the M-phase-promoting factor (MPF). Once activated, MPF is sustained until mitotic spindle assembly by phosphorylation-dependent feedback loops that prevent inhibitory phosphorylation of cdk1 and ubiquitin-dependent degradation of cyclin B. Whether subsequent MPF inactivation and anaphase onset require a specific phosphatase(s) to reverse these feedback loops is not known. Here we show through biochemical and genetic evidence that timely MPF inactivation requires activity of the essential RNA polymerase II-carboxy-terminal domain phosphatase Fcp1, in a transcription-independent manner. We identify Cdc20, a coactivator of the ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C) required for cyclin degradation and anaphase onset, USP44, a deubiquitinating peptidase that opposes APC/C action, and Wee1, a cdk1 inhibitory kinase, as relevant Fcp1 targets. We propose that Fcp1 has a crucial role in the liaison between dephosphorylation and ubiquitination that drives mitosis exit. Nature Pub. Group 2012-06-12 /pmc/articles/PMC3621406/ /pubmed/22692537 http://dx.doi.org/10.1038/ncomms1886 Text en Copyright © 2012, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
spellingShingle Article
Visconti, Roberta
Palazzo, Luca
Della Monica, Rosa
Grieco, Domenico
Fcp1-dependent dephosphorylation is required for M-phase-promoting factor inactivation at mitosis exit
title Fcp1-dependent dephosphorylation is required for M-phase-promoting factor inactivation at mitosis exit
title_full Fcp1-dependent dephosphorylation is required for M-phase-promoting factor inactivation at mitosis exit
title_fullStr Fcp1-dependent dephosphorylation is required for M-phase-promoting factor inactivation at mitosis exit
title_full_unstemmed Fcp1-dependent dephosphorylation is required for M-phase-promoting factor inactivation at mitosis exit
title_short Fcp1-dependent dephosphorylation is required for M-phase-promoting factor inactivation at mitosis exit
title_sort fcp1-dependent dephosphorylation is required for m-phase-promoting factor inactivation at mitosis exit
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3621406/
https://www.ncbi.nlm.nih.gov/pubmed/22692537
http://dx.doi.org/10.1038/ncomms1886
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