PHD1 links cell-cycle progression to oxygen sensing through hydroxylation of the centrosomal protein Cep192

Moser, Sandra C., Bensaddek, Dalila, Ortmann, Brian, Maure, Jean-Francois, Mudie, Sharon, Blow, J. Julian ORCID: https://orcid.org/0000-0002-9524-5849, Lamond, Angus I., Swedlow, Jason R. and Rocha, Sonia (2013) PHD1 links cell-cycle progression to oxygen sensing through hydroxylation of the centrosomal protein Cep192. Developmental Cell, 26 (4). pp. 381-392. ISSN 1878-1551

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Abstract

PHD1 belongs to the family of prolyl-4-hydroxylases (PHDs) that is responsible for posttranslational modification of prolines on specific target proteins. Because PHD activity is sensitive to oxygen levels and certain byproducts of the tricarboxylic acid cycle, PHDs act as sensors of the cell's metabolic state. Here, we identify PHD1 as a critical molecular link between oxygen sensing and cell-cycle control. We show that PHD1 function is required for centrosome duplication and maturation through modification of the critical centrosome component Cep192. Importantly, PHD1 is also required for primary cilia formation. Cep192 is hydroxylated by PHD1 on proline residue 1717. This hydroxylation is required for binding of the E3 ubiquitin ligase SCF(Skp2), which ubiquitinates Cep192, targeting it for proteasomal degradation. By modulating Cep192 levels, PHD1 thereby affects the processes of centriole duplication and centrosome maturation and contributes to the regulation of cell-cycle progression.

Item Type:	Article
Additional Information:	Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.
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Depositing User:	LivePure Connector
Date Deposited:	10 Jun 2024 15:30
Last Modified:	25 Sep 2024 17:51
URI:	https://ueaeprints.uea.ac.uk/id/eprint/95465
DOI:	10.1016/j.devcel.2013.06.014

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