The SKP1-Cullin-F-box E3 ligase βTrCP and CDK2 cooperate to control STIL abundance and centriole number

Arquint, Christian and Cubizolles, Fabien and Morand, Agathe and Schmidt, Alexander and Nigg, Erich A.. (2018) The SKP1-Cullin-F-box E3 ligase βTrCP and CDK2 cooperate to control STIL abundance and centriole number. Open biology, 8 (2). p. 16.

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Official URL: https://edoc.unibas.ch/61054/

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Deregulation of centriole duplication has been implicated in cancer and primary microcephaly. Accordingly, it is important to understand how key centriole duplication factors are regulated. E3 ubiquitin ligases have been implicated in controlling the levels of several duplication factors, including PLK4, STIL and SAS-6, but the precise mechanisms ensuring centriole homeostasis remain to be fully understood. Here, we have combined proteomics approaches with the use of MLN4924, a generic inhibitor of SCF E3 ubiquitin ligases, to monitor changes in the cellular abundance of centriole duplication factors. We identified human STIL as a novel substrate of SCF-βTrCP. The binding of βTrCP depends on a DSG motif within STIL, and serine 395 within this motif is phosphorylated; in vivo; SCF-βTrCP-mediated degradation of STIL occurs throughout interphase and mutations in the DSG motif causes massive centrosome amplification, attesting to the physiological importance of the pathway. We also uncover a connection between this new pathway and CDK2, whose role in centriole biogenesis remains poorly understood. We show that CDK2 activity protects STIL against SCF-βTrCP-mediated degradation, indicating that CDK2 and SCF-βTrCP cooperate via STIL to control centriole biogenesis.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Cell Biology (Nigg)
UniBasel Contributors:Nigg, Erich A. and Arquint, Christian and Cubizolles, Fabien and Schmidt, Alexander
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:29 Apr 2020 11:39
Deposited On:29 Apr 2020 11:39

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