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

Mara Esposito, H Begum Akman, Philippe Giron, M Angeles Ceregido, Rogier Schepers, Luis C Ramos Paez, Esther La Monaca, Jacques De Greve, Olivier Coux, Carl De Trez, Catherine Lindon, Gustavo J Gutierrez

Onderzoeksoutput: Articlepeer review

14 Citaten (Scopus)

Samenvatting

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.

Originele taal-2English
Pagina's (van-tot)6009-6023
Aantal pagina's15
TijdschriftOncogene
Volume39
Nummer van het tijdschrift37
DOI's
StatusPublished - sep 2020

Vingerafdruk

Duik in de onderzoeksthema's van 'USP13 controls the stability of Aurora B impacting progression through the cell cycle'. Samen vormen ze een unieke vingerafdruk.

Citeer dit