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Ordered dephosphorylation initiated by the selective proteolysis of cyclin B drives mitotic exit
APC/C-mediated proteolysis of cyclin B and securin promotes anaphase entry, inactivating CDK1 and permitting chromosome segregation, respectively. Reduction of CDK1 activity relieves inhibition of the CDK1-counteracting phosphatases PP1 and PP2A-B55, allowing wide-spread dephosphorylation of substra...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529458/ https://www.ncbi.nlm.nih.gov/pubmed/32869743 http://dx.doi.org/10.7554/eLife.59885 |
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author | Holder, James Mohammed, Shabaz Barr, Francis A |
author_facet | Holder, James Mohammed, Shabaz Barr, Francis A |
author_sort | Holder, James |
collection | PubMed |
description | APC/C-mediated proteolysis of cyclin B and securin promotes anaphase entry, inactivating CDK1 and permitting chromosome segregation, respectively. Reduction of CDK1 activity relieves inhibition of the CDK1-counteracting phosphatases PP1 and PP2A-B55, allowing wide-spread dephosphorylation of substrates. Meanwhile, continued APC/C activity promotes proteolysis of other mitotic regulators. Together, these activities orchestrate a complex series of events during mitotic exit. However, the relative importance of regulated proteolysis and dephosphorylation in dictating the order and timing of these events remains unclear. Using high temporal-resolution proteomics, we compare the relative extent of proteolysis and protein dephosphorylation. This reveals highly-selective rapid proteolysis of cyclin B, securin and geminin at the metaphase-anaphase transition, followed by slow proteolysis of other substrates. Dephosphorylation requires APC/C-dependent destruction of cyclin B and was resolved into PP1-dependent categories with unique sequence motifs. We conclude that dephosphorylation initiated by selective proteolysis of cyclin B drives the bulk of changes observed during mitotic exit. |
format | Online Article Text |
id | pubmed-7529458 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-75294582020-10-05 Ordered dephosphorylation initiated by the selective proteolysis of cyclin B drives mitotic exit Holder, James Mohammed, Shabaz Barr, Francis A eLife Cell Biology APC/C-mediated proteolysis of cyclin B and securin promotes anaphase entry, inactivating CDK1 and permitting chromosome segregation, respectively. Reduction of CDK1 activity relieves inhibition of the CDK1-counteracting phosphatases PP1 and PP2A-B55, allowing wide-spread dephosphorylation of substrates. Meanwhile, continued APC/C activity promotes proteolysis of other mitotic regulators. Together, these activities orchestrate a complex series of events during mitotic exit. However, the relative importance of regulated proteolysis and dephosphorylation in dictating the order and timing of these events remains unclear. Using high temporal-resolution proteomics, we compare the relative extent of proteolysis and protein dephosphorylation. This reveals highly-selective rapid proteolysis of cyclin B, securin and geminin at the metaphase-anaphase transition, followed by slow proteolysis of other substrates. Dephosphorylation requires APC/C-dependent destruction of cyclin B and was resolved into PP1-dependent categories with unique sequence motifs. We conclude that dephosphorylation initiated by selective proteolysis of cyclin B drives the bulk of changes observed during mitotic exit. eLife Sciences Publications, Ltd 2020-09-01 /pmc/articles/PMC7529458/ /pubmed/32869743 http://dx.doi.org/10.7554/eLife.59885 Text en © 2020, Holder et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Cell Biology Holder, James Mohammed, Shabaz Barr, Francis A Ordered dephosphorylation initiated by the selective proteolysis of cyclin B drives mitotic exit |
title | Ordered dephosphorylation initiated by the selective proteolysis of cyclin B drives mitotic exit |
title_full | Ordered dephosphorylation initiated by the selective proteolysis of cyclin B drives mitotic exit |
title_fullStr | Ordered dephosphorylation initiated by the selective proteolysis of cyclin B drives mitotic exit |
title_full_unstemmed | Ordered dephosphorylation initiated by the selective proteolysis of cyclin B drives mitotic exit |
title_short | Ordered dephosphorylation initiated by the selective proteolysis of cyclin B drives mitotic exit |
title_sort | ordered dephosphorylation initiated by the selective proteolysis of cyclin b drives mitotic exit |
topic | Cell Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529458/ https://www.ncbi.nlm.nih.gov/pubmed/32869743 http://dx.doi.org/10.7554/eLife.59885 |
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