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...
Autores principales: | , , , |
---|---|
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 |