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Budding yeast PAK kinases regulate mitotic exit by two different mechanisms

We report the characterization of the dominant-negative CLA4t allele of the budding yeast CLA4 gene, encoding a member of the p21-activated kinase (PAK) family of protein kinases, which, together with its homologue STE20, plays an essential role in promoting budding and cytokinesis. Overproduction o...

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Detalles Bibliográficos
Autores principales: Chiroli, Elena, Fraschini, Roberta, Beretta, Alessia, Tonelli, Mariagrazia, Lucchini, Giovanna, Piatti, Simonetta
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2003
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2173773/
https://www.ncbi.nlm.nih.gov/pubmed/12642613
http://dx.doi.org/10.1083/jcb.200209097
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author Chiroli, Elena
Fraschini, Roberta
Beretta, Alessia
Tonelli, Mariagrazia
Lucchini, Giovanna
Piatti, Simonetta
author_facet Chiroli, Elena
Fraschini, Roberta
Beretta, Alessia
Tonelli, Mariagrazia
Lucchini, Giovanna
Piatti, Simonetta
author_sort Chiroli, Elena
collection PubMed
description We report the characterization of the dominant-negative CLA4t allele of the budding yeast CLA4 gene, encoding a member of the p21-activated kinase (PAK) family of protein kinases, which, together with its homologue STE20, plays an essential role in promoting budding and cytokinesis. Overproduction of the Cla4t protein likely inhibits both endogenous Cla4 and Ste20 and causes a delay in the onset of anaphase that correlates with inactivation of Cdc20/anaphase-promoting complex (APC)–dependent proteolysis of both the cyclinB Clb2 and securin. Although the precise mechanism of APC inhibition by Cla4t remains to be elucidated, our results suggest that Cla4 and Ste20 may regulate the first wave of cyclinB proteolysis mediated by Cdc20/APC, which has been shown to be crucial for activation of the mitotic exit network (MEN). We show that the Cdk1-inhibitory kinase Swe1 is required for the Cla4t-dependent delay in cell cycle progression, suggesting that it might be required to prevent full Cdc20/APC and MEN activation. In addition, inhibition of PAK kinases by Cla4t prevents mitotic exit also by a Swe1-independent mechanism impinging directly on the MEN activator Tem1.
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spelling pubmed-21737732008-05-01 Budding yeast PAK kinases regulate mitotic exit by two different mechanisms Chiroli, Elena Fraschini, Roberta Beretta, Alessia Tonelli, Mariagrazia Lucchini, Giovanna Piatti, Simonetta J Cell Biol Article We report the characterization of the dominant-negative CLA4t allele of the budding yeast CLA4 gene, encoding a member of the p21-activated kinase (PAK) family of protein kinases, which, together with its homologue STE20, plays an essential role in promoting budding and cytokinesis. Overproduction of the Cla4t protein likely inhibits both endogenous Cla4 and Ste20 and causes a delay in the onset of anaphase that correlates with inactivation of Cdc20/anaphase-promoting complex (APC)–dependent proteolysis of both the cyclinB Clb2 and securin. Although the precise mechanism of APC inhibition by Cla4t remains to be elucidated, our results suggest that Cla4 and Ste20 may regulate the first wave of cyclinB proteolysis mediated by Cdc20/APC, which has been shown to be crucial for activation of the mitotic exit network (MEN). We show that the Cdk1-inhibitory kinase Swe1 is required for the Cla4t-dependent delay in cell cycle progression, suggesting that it might be required to prevent full Cdc20/APC and MEN activation. In addition, inhibition of PAK kinases by Cla4t prevents mitotic exit also by a Swe1-independent mechanism impinging directly on the MEN activator Tem1. The Rockefeller University Press 2003-03-17 /pmc/articles/PMC2173773/ /pubmed/12642613 http://dx.doi.org/10.1083/jcb.200209097 Text en Copyright © 2003, 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 Article
Chiroli, Elena
Fraschini, Roberta
Beretta, Alessia
Tonelli, Mariagrazia
Lucchini, Giovanna
Piatti, Simonetta
Budding yeast PAK kinases regulate mitotic exit by two different mechanisms
title Budding yeast PAK kinases regulate mitotic exit by two different mechanisms
title_full Budding yeast PAK kinases regulate mitotic exit by two different mechanisms
title_fullStr Budding yeast PAK kinases regulate mitotic exit by two different mechanisms
title_full_unstemmed Budding yeast PAK kinases regulate mitotic exit by two different mechanisms
title_short Budding yeast PAK kinases regulate mitotic exit by two different mechanisms
title_sort budding yeast pak kinases regulate mitotic exit by two different mechanisms
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2173773/
https://www.ncbi.nlm.nih.gov/pubmed/12642613
http://dx.doi.org/10.1083/jcb.200209097
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