Cargando…

Human Cdc14A regulates Wee1 stability by counteracting CDK-mediated phosphorylation

The activity of Cdk1–cyclin B1 mitotic complexes is regulated by the balance between the counteracting activities of Wee1/Myt1 kinases and Cdc25 phosphatases. These kinases and phosphatases must be strictly regulated to ensure proper mitotic timing. One masterpiece of this regulatory network is Cdk1...

Descripción completa

Detalles Bibliográficos
Autores principales: Ovejero, Sara, Ayala, Patricia, Bueno, Avelino, Sacristán, María P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3510014/
https://www.ncbi.nlm.nih.gov/pubmed/23051732
http://dx.doi.org/10.1091/mbc.E12-04-0260
_version_ 1782251400475967488
author Ovejero, Sara
Ayala, Patricia
Bueno, Avelino
Sacristán, María P.
author_facet Ovejero, Sara
Ayala, Patricia
Bueno, Avelino
Sacristán, María P.
author_sort Ovejero, Sara
collection PubMed
description The activity of Cdk1–cyclin B1 mitotic complexes is regulated by the balance between the counteracting activities of Wee1/Myt1 kinases and Cdc25 phosphatases. These kinases and phosphatases must be strictly regulated to ensure proper mitotic timing. One masterpiece of this regulatory network is Cdk1, which promotes Cdc25 activity and suppresses inhibitory Wee1/Myt1 kinases through direct phosphorylation. The Cdk1-dependent phosphorylation of Wee1 primes phosphorylation by additional kinases such as Plk1, triggering Wee1 degradation at the onset of mitosis. Here we report that Cdc14A plays an important role in the regulation of Wee1 stability. Depletion of Cdc14A results in a significant reduction in Wee1 protein levels. Cdc14A binds to Wee1 at its amino-terminal domain and reverses CDK-mediated Wee1 phosphorylation. In particular, we found that Cdc14A inhibits Wee1 degradation through the dephosphorylation of Ser-123 and Ser-139 residues. Thus the lack of phosphorylation of these two residues prevents the interaction with Plk1 and the consequent efficient Wee1 degradation at the onset of mitosis. These data support the hypothesis that Cdc14A counteracts Cdk1–cyclin B1 activity through Wee1 dephosphorylation.
format Online
Article
Text
id pubmed-3510014
institution National Center for Biotechnology Information
language English
publishDate 2012
publisher The American Society for Cell Biology
record_format MEDLINE/PubMed
spelling pubmed-35100142013-02-16 Human Cdc14A regulates Wee1 stability by counteracting CDK-mediated phosphorylation Ovejero, Sara Ayala, Patricia Bueno, Avelino Sacristán, María P. Mol Biol Cell Articles The activity of Cdk1–cyclin B1 mitotic complexes is regulated by the balance between the counteracting activities of Wee1/Myt1 kinases and Cdc25 phosphatases. These kinases and phosphatases must be strictly regulated to ensure proper mitotic timing. One masterpiece of this regulatory network is Cdk1, which promotes Cdc25 activity and suppresses inhibitory Wee1/Myt1 kinases through direct phosphorylation. The Cdk1-dependent phosphorylation of Wee1 primes phosphorylation by additional kinases such as Plk1, triggering Wee1 degradation at the onset of mitosis. Here we report that Cdc14A plays an important role in the regulation of Wee1 stability. Depletion of Cdc14A results in a significant reduction in Wee1 protein levels. Cdc14A binds to Wee1 at its amino-terminal domain and reverses CDK-mediated Wee1 phosphorylation. In particular, we found that Cdc14A inhibits Wee1 degradation through the dephosphorylation of Ser-123 and Ser-139 residues. Thus the lack of phosphorylation of these two residues prevents the interaction with Plk1 and the consequent efficient Wee1 degradation at the onset of mitosis. These data support the hypothesis that Cdc14A counteracts Cdk1–cyclin B1 activity through Wee1 dephosphorylation. The American Society for Cell Biology 2012-12-01 /pmc/articles/PMC3510014/ /pubmed/23051732 http://dx.doi.org/10.1091/mbc.E12-04-0260 Text en © 2012 Ovejero et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Ovejero, Sara
Ayala, Patricia
Bueno, Avelino
Sacristán, María P.
Human Cdc14A regulates Wee1 stability by counteracting CDK-mediated phosphorylation
title Human Cdc14A regulates Wee1 stability by counteracting CDK-mediated phosphorylation
title_full Human Cdc14A regulates Wee1 stability by counteracting CDK-mediated phosphorylation
title_fullStr Human Cdc14A regulates Wee1 stability by counteracting CDK-mediated phosphorylation
title_full_unstemmed Human Cdc14A regulates Wee1 stability by counteracting CDK-mediated phosphorylation
title_short Human Cdc14A regulates Wee1 stability by counteracting CDK-mediated phosphorylation
title_sort human cdc14a regulates wee1 stability by counteracting cdk-mediated phosphorylation
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3510014/
https://www.ncbi.nlm.nih.gov/pubmed/23051732
http://dx.doi.org/10.1091/mbc.E12-04-0260
work_keys_str_mv AT ovejerosara humancdc14aregulateswee1stabilitybycounteractingcdkmediatedphosphorylation
AT ayalapatricia humancdc14aregulateswee1stabilitybycounteractingcdkmediatedphosphorylation
AT buenoavelino humancdc14aregulateswee1stabilitybycounteractingcdkmediatedphosphorylation
AT sacristanmariap humancdc14aregulateswee1stabilitybycounteractingcdkmediatedphosphorylation