Human Cdc14A Phosphatase Modulates the G2/M Transition through Cdc25A and Cdc25B
| Autor: | María P. Sacristán, Avelino Bueno, María D. Vázquez-Novelle, Sara Ovejero, Niels Mailand |
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| Rok vydání: | 2010 |
| Předmět: |
G2 Phase
CDC25A Cdc25 Mitosis Hardware_PERFORMANCEANDRELIABILITY Saccharomyces cerevisiae Polo-like kinase Biochemistry Cell Line Cyclin-dependent kinase Cyclins Phosphatase CDC2 Protein Kinase Hardware_INTEGRATEDCIRCUITS Humans cdc25 Phosphatases Molecular Biology CDK (cyclin-dependent kinase) Cdc14A Cyclin-dependent kinase 1 biology Cdc14 Cell Cycle Cell Biology Phosphoric Monoester Hydrolases Cell biology Enzyme Activation biology.protein Protein Tyrosine Phosphatases biological phenomena cell phenomena and immunity |
| Zdroj: | The Journal of Biological Chemistry Digital.CSIC. Repositorio Institucional del CSIC instname |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m110.133009 |
| Popis: | Free via Open Access: OA and Free via Creative Commons: Creative Commons Attribution Non-Commercial License applies to Author Choice Articles. The Cdc14 family of serine-threonine phosphatases antagonizes CDK activity by reversing CDK-dependent phosphorylation events. It is well established that the yeast members of this family bring about the M/G1 transition. Budding yeast Cdc14 is essential for CDK inactivation at the end of mitosis and fission yeast Cdc14 homologue Flp1/Clp1 down-regulates Cdc25 to ensure the inactivation of mitotic CDK complexes to trigger cell division. However, the functions of human Cdc14 homologues remain poorly understood. Here we have tested the hypothesis that Cdc14A might regulate Cdc25 mitotic inducers in human cells. We found that increasing levels of Cdc14A delay entry into mitosis by inhibiting Cdk1-cyclin B1 activity. By contrast, lowering the levels of Cdc14A accelerates mitotic entry. Biochemical analyses revealed that Cdc14A acts through key Cdk1-cyclin B1 regulators. We observed that Cdc14A directly bound to and dephosphorylated Cdc25B, inhibiting its catalytic activity. Cdc14A also regulated the activity of Cdc25A at the G2/M transition. Our results indicate that Cdc14A phosphatase prevents premature activation of Cdk1 regulating Cdc25A and Cdc25B at the entry into mitosis. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc. This work was supported by Grants BFU2006-05878/BFU2008-04293 from Spanish Ministerio de Educación y Ciencia (MEC) and SAN196/SA32/07 from Junta Castilla y León. |
| Databáze: | OpenAIRE |
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