Cdc14 activation requires coordinated Cdk1-dependent phosphorylation of Net1 and PP2A-Cdc55 at anaphase onset
| Autor: | Ines Calabria, Yolanda Moyano-Rodriguez, Soraya Játiva, Ethel Queralt, Patricia García |
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| Přispěvatelé: | Ministerio de Economía, Industria y Competitividad (España), European Commission, Instituto de Salud Carlos III, Queralt, Ethel, Queralt, Ethel [0000-0003-0045-0039] |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Phosphopeptides
Saccharomyces cerevisiae Proteins Mitosis Cell Cycle Proteins Saccharomyces cerevisiae Cell cycle FEAR environment and public health Zds1 03 medical and health sciences Cellular and Molecular Neuroscience Tandem Mass Spectrometry Cyclin-dependent kinase CDC2 Protein Kinase Humans Protein Phosphatase 2 Phosphorylation Molecular Biology Metaphase Chromatography High Pressure Liquid Separase Anaphase Cell Nucleus Pharmacology 0303 health sciences biology Chemistry Cdc14 030302 biochemistry & molecular biology PP2A–Cdc55 Phosphatases Nuclear Proteins Cell Biology Protein phosphatase 2 Mitotic exit Cell biology biology.protein Molecular Medicine Protein Tyrosine Phosphatases CDC28 Protein Kinase S cerevisiae |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| Popis: | 59 páginas 5 figuras, 1 tabla Exit from mitosis and completion of cytokinesis require the inactivation of mitotic cyclin-dependent kinase (Cdk) activity. In budding yeast, Cdc14 phosphatase is a key mitotic regulator that is activated in anaphase to counteract Cdk activity. In metaphase, Cdc14 is kept inactive in the nucleolus, where it is sequestered by its inhibitor, Net1. At anaphase onset, downregulation of PP2ACdc55 phosphatase by separase and Zds1 protein promotes Net1 phosphorylation and, consequently, Cdc14 release from the nucleolus. The mechanism by which PP2ACdc55 activity is downregulated during anaphase remains to be elucidated. Here, we demonstrate that Cdc55 regulatory subunit is phosphorylated in anaphase in a Cdk1-Clb2-dependent manner. Interestingly, cdc55-ED phosphomimetic mutant inactivates PP2ACdc55 phosphatase activity towards Net1 and promotes Cdc14 activation. Separase and Zds1 facilitate Cdk-dependent Net1 phosphorylation and Cdc14 release from the nucleolus by modulating PP2ACdc55 activity via Cdc55 phosphorylation. In addition, human Cdk1-CyclinB1 phosphorylates human B55, indicating that the mechanism is conserved in higher eukaryotes. We thank CERCA Program/Generalitat de Catalunya for institutional support. Our laboratory is funded by the Spanish Ministry of Economy, Industry and Competitiveness (MINECO), which is part of the State Agency, through the projects BFU2013-43132-P and BFU2016-77975-R, (co-funded by the European Regional Development Fund, ERDF, a way to build Europe). The proteomics analyses were performed in the IDIBELL Clinical Proteomics Unit which is part of Proteored, PRB3 and is supported by Grant PT17/0019, of the PE I+D+i 2013-2016, funded by ISCIII and ERDF |
| Databáze: | OpenAIRE |
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