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

被引：24

作者：

Esposito, Mara ^{[1
]}

Akman, H. Begum ^{[2
]}

Giron, Philippe ^{[1
,3
]}

Ceregido, M. Angeles ^{[1
,6
]}

Schepers, Rogier ^{[1
,7
]}

Ramos Paez, Luis C. ^{[1
,8
]}

La Monaca, Esther ^{[1
,9
]}

De Greve, Jacques ^{[3
]}

Coux, Olivier ^{[4
]}

De Trez, Carl ^{[5
]}

Lindon, Catherine ^{[2
]}

Gutierrez, Gustavo J. ^{[1
,10
]}

机构：

[1] Vrije Univ Brussel, Fac Sci & Bioengn Sci, Dept Biol, Lab Pathophysiol Cell Signaling, Pl Laan 2, B-1050 Brussels, Belgium

[2] Univ Cambridge, Dept Pharmacol, Tennis Court Rd, Cambridge CB2 1PD, England

[3] Vrije Univ Brussel, Fac Med & Pharm, Lab Mol & Med Oncol, Laarbeeklaan 103, B-1090 Brussels, Belgium

[4] CNRS, CRBM, 1919 Route Mende, F-34293 Montpellier, France

[5] Vrije Univ Brussel, Fac Sci & Bioengn Sci, Dept Bioengn, Lab Cellular & Mol Immunol, Pl Laan 2, B-1050 Brussels, Belgium

[6] GlaxoSmithKline, Ave Pascal 2-4-6, B-1300 Wavre, Belgium

[7] VIB KU Leuven, Ctr Canc Biol, Campus Gasthuisberg,Herestr 49-B912, Leuven, Belgium

[8] Ablynx NV, Technol Pk 21, B-9052 Ghent, Belgium

[9] Janssen Pharmaceut NV, Turnhoutseweg 30, B-2340 Beerse, Belgium

[10] Galapagos NV, Generaal Wittelaan L11 A3, B-2800 Mechelen, Belgium

来源：

ONCOGENE | 2020年 / 39卷 / 37期

基金：

英国生物技术与生命科学研究理事会;

关键词：

TUMOR-SUPPRESSOR CYLD; MITOTIC KINASE; OVEREXPRESSION; ANEUPLOIDY; PHOSPHORYLATION; DEGRADATION; EXPRESSION; PREDICTION; REGULATOR; SEQUENCE;

D O I：

10.1038/s41388-020-01396-8

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：6009 / 6023

页数：15

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