USP13 controls the stability of Aurora B impacting progression through the cell cycle
| Autor: | Catherine Lindon, Rogier Schepers, Philippe Giron, Jacques De Greve, H Begum Akman, M Angeles Ceregido, Luis C Ramos Paez, Esther La Monaca, Carl De Trez, Mara Esposito, Olivier Coux, Gustavo J. Gutierrez |
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| Přispěvatelé: | Centre de recherche en Biologie Cellulaire (CRBM), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Faculty of Sciences and Bioengineering Sciences, Biology, Medical Genetics, Basic (bio-) Medical Sciences, Faculty of Medicine and Pharmacy, Clinical sciences, Laboratory for Medical and Molecular Oncology, Department of Bio-engineering Sciences, Cellular and Molecular Immunology |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research Cell division [SDV]Life Sciences [q-bio] Aurora B kinase Gene Expression macromolecular substances Deubiquitinating enzyme 03 medical and health sciences 0302 clinical medicine Ubiquitin Cell Line Tumor Endopeptidases Enzyme Stability Serine Genetics Aurora Kinase B Humans Phosphorylation Molecular Biology Mitosis ComputingMilieux_MISCELLANEOUS biology Cell Cycle Cell Cycle Checkpoints Cell cycle Ubiquitin ligase Cell biology enzymes and coenzymes (carbohydrates) 030104 developmental biology Gene Knockdown Techniques 030220 oncology & carcinogenesis embryonic structures Disease Progression biology.protein Interphase Ubiquitin-Specific Proteases biological phenomena cell phenomena and immunity Protein Binding |
| Zdroj: | Oncogene Oncogene, Nature Publishing Group, 2020, 39 (37), pp.6009-6023. ⟨10.1038/s41388-020-01396-8⟩ |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/s41388-020-01396-8 |
| Popis: | Aurora B kinase plays essential roles in mitosis. Its protein levels increase before the onset of mitosis and sharply decrease during mitosis exit. The latter decrease is due to a balance between the actions of the E3 ubiquitin ligase anaphase-promoting complex or cyclosome (activated by the Cdh1 adapter), and the deubiquitinating enzyme USP35. Aurora B also executes important functions in interphase. Abnormal modulation of Aurora B in interphase leads to cell cycle defects often linked to aberrant chromosomal condensation and segregation. Very little is however known about how Aurora B levels are regulated in interphase. Here we found that USP13-associates with and stabilizes Aurora B in cells, especially before their entry into mitosis. In order for USP13 to exert its stabilizing effect on Aurora B, their association is promoted by the Aurora B-mediated phosphorylation of USP13 at Serine 114. We also present evidence that USP13 instigates Aurora B deubiquitination and/or protect it from degradation in a non-catalytic manner. In addition, we report that genetic or chemical modulation of the cellular levels/activity of USP13 affects unperturbed cell-cycle progression. Overall our study unveils the molecular and cellular connections of the USP13-Aurora B axis, which potentially participates in the rewiring of the cell cycle happening in cancer cells. |
| Databáze: | OpenAIRE |
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