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USP13 controls the stability of Aurora B impacting progression through the cell cycle.
- Source :
-
Oncogene [Oncogene] 2020 Sep; Vol. 39 (37), pp. 6009-6023. Date of Electronic Publication: 2020 Aug 08. - Publication Year :
- 2020
-
Abstract
- 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.
- Subjects :
- Cell Cycle Checkpoints genetics
Cell Line, Tumor
Disease Progression
Endopeptidases metabolism
Enzyme Stability
Gene Expression
Gene Knockdown Techniques
Humans
Phosphorylation
Protein Binding
Serine metabolism
Ubiquitin-Specific Proteases
Aurora Kinase B metabolism
Cell Cycle genetics
Endopeptidases genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1476-5594
- Volume :
- 39
- Issue :
- 37
- Database :
- MEDLINE
- Journal :
- Oncogene
- Publication Type :
- Academic Journal
- Accession number :
- 32772043
- Full Text :
- https://doi.org/10.1038/s41388-020-01396-8