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Mitosis persists in the absence of Cdk1 activity when proteolysis or protein phosphatase activity is suppressed
Cellular transition to anaphase and mitotic exit has been linked to the loss of cyclin-dependent kinase 1 (Cdk1) kinase activity as a result of anaphase-promoting complex/cyclosome (APC/C)–dependent specific degradation of its cyclin B1 subunit. Cdk1 inhibition by roscovitine is known to induce prem...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2007
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2080905/ https://www.ncbi.nlm.nih.gov/pubmed/18025303 http://dx.doi.org/10.1083/jcb.200704117 |
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author | Skoufias, Dimitrios A. Indorato, Rose-Laure Lacroix, Françoise Panopoulos, Andreas Margolis, Robert L. |
author_facet | Skoufias, Dimitrios A. Indorato, Rose-Laure Lacroix, Françoise Panopoulos, Andreas Margolis, Robert L. |
author_sort | Skoufias, Dimitrios A. |
collection | PubMed |
description | Cellular transition to anaphase and mitotic exit has been linked to the loss of cyclin-dependent kinase 1 (Cdk1) kinase activity as a result of anaphase-promoting complex/cyclosome (APC/C)–dependent specific degradation of its cyclin B1 subunit. Cdk1 inhibition by roscovitine is known to induce premature mitotic exit, whereas inhibition of the APC/C-dependent degradation of cyclin B1 by MG132 induces mitotic arrest. In this study, we find that combining both drugs causes prolonged mitotic arrest in the absence of Cdk1 activity. Different Cdk1 and proteasome inhibitors produce similar results, indicating that the effect is not drug specific. We verify mitotic status by the retention of mitosis-specific markers and Cdk1 phosphorylation substrates, although cells can undergo late mitotic furrowing while still in mitosis. Overall, we conclude that continuous Cdk1 activity is not essential to maintain the mitotic state and that phosphatase activity directed at Cdk1 substrates is largely quiescent during mitosis. Furthermore, the degradation of a protein other than cyclin B1 is essential to activate a phosphatase that, in turn, enables mitotic exit. |
format | Text |
id | pubmed-2080905 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-20809052008-05-19 Mitosis persists in the absence of Cdk1 activity when proteolysis or protein phosphatase activity is suppressed Skoufias, Dimitrios A. Indorato, Rose-Laure Lacroix, Françoise Panopoulos, Andreas Margolis, Robert L. J Cell Biol Research Articles Cellular transition to anaphase and mitotic exit has been linked to the loss of cyclin-dependent kinase 1 (Cdk1) kinase activity as a result of anaphase-promoting complex/cyclosome (APC/C)–dependent specific degradation of its cyclin B1 subunit. Cdk1 inhibition by roscovitine is known to induce premature mitotic exit, whereas inhibition of the APC/C-dependent degradation of cyclin B1 by MG132 induces mitotic arrest. In this study, we find that combining both drugs causes prolonged mitotic arrest in the absence of Cdk1 activity. Different Cdk1 and proteasome inhibitors produce similar results, indicating that the effect is not drug specific. We verify mitotic status by the retention of mitosis-specific markers and Cdk1 phosphorylation substrates, although cells can undergo late mitotic furrowing while still in mitosis. Overall, we conclude that continuous Cdk1 activity is not essential to maintain the mitotic state and that phosphatase activity directed at Cdk1 substrates is largely quiescent during mitosis. Furthermore, the degradation of a protein other than cyclin B1 is essential to activate a phosphatase that, in turn, enables mitotic exit. The Rockefeller University Press 2007-11-19 /pmc/articles/PMC2080905/ /pubmed/18025303 http://dx.doi.org/10.1083/jcb.200704117 Text en Copyright © 2007, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Skoufias, Dimitrios A. Indorato, Rose-Laure Lacroix, Françoise Panopoulos, Andreas Margolis, Robert L. Mitosis persists in the absence of Cdk1 activity when proteolysis or protein phosphatase activity is suppressed |
title | Mitosis persists in the absence of Cdk1 activity when proteolysis or protein phosphatase activity is suppressed |
title_full | Mitosis persists in the absence of Cdk1 activity when proteolysis or protein phosphatase activity is suppressed |
title_fullStr | Mitosis persists in the absence of Cdk1 activity when proteolysis or protein phosphatase activity is suppressed |
title_full_unstemmed | Mitosis persists in the absence of Cdk1 activity when proteolysis or protein phosphatase activity is suppressed |
title_short | Mitosis persists in the absence of Cdk1 activity when proteolysis or protein phosphatase activity is suppressed |
title_sort | mitosis persists in the absence of cdk1 activity when proteolysis or protein phosphatase activity is suppressed |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2080905/ https://www.ncbi.nlm.nih.gov/pubmed/18025303 http://dx.doi.org/10.1083/jcb.200704117 |
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