USP13 controls the stability of Aurora B impacting progression through the cell cycle

• Published in: Oncogene Vol. 39; no. 37; pp. 6009 - 6023
• Main Authors: Esposito, Mara, Akman, H. Begum, Giron, Philippe, Ceregido, M. Angeles, Schepers, Rogier, Ramos Paez, Luis C., La Monaca, Esther, De Greve, Jacques, Coux, Olivier, De Trez, Carl, Lindon, Catherine, Gutierrez, Gustavo J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10.09.2020; Nature Publishing Group; Nature Publishing Group [1987-....]
• Subjects: 631/337/641; 631/45/474/582; Anaphase; Anaphase-promoting complex; Apoptosis; Aurora B protein; Aurora Kinase B - metabolism; Cell Biology; Cell cycle; Cell Cycle - genetics; Cell Cycle Checkpoints - genetics; Cell Line, Tumor; Disease Progression; E-cadherin; Endopeptidases - genetics; Endopeptidases - metabolism; Enzyme Stability; Gene Expression; Gene Knockdown Techniques; Human Genetics; Humans; Internal Medicine; Interphase; Kinases; Life Sciences; Ligases; Medicine; Medicine & Public Health; Mitosis; Oncology; Phosphorylation; Protein Binding; Serine; Serine - metabolism; Ubiquitin; Ubiquitin-protein ligase
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/s41388-020-01396-8

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.