Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Skoufias, Dimitrios A., Indorato, Rose-Laure, Lacroix, Françoise, Panopoulos, Andreas, Margolis, Robert L.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2007
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
_version_ 1782138151608778752
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
work_keys_str_mv AT skoufiasdimitriosa mitosispersistsintheabsenceofcdk1activitywhenproteolysisorproteinphosphataseactivityissuppressed
AT indoratoroselaure mitosispersistsintheabsenceofcdk1activitywhenproteolysisorproteinphosphataseactivityissuppressed
AT lacroixfrancoise mitosispersistsintheabsenceofcdk1activitywhenproteolysisorproteinphosphataseactivityissuppressed
AT panopoulosandreas mitosispersistsintheabsenceofcdk1activitywhenproteolysisorproteinphosphataseactivityissuppressed
AT margolisrobertl mitosispersistsintheabsenceofcdk1activitywhenproteolysisorproteinphosphataseactivityissuppressed