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MBC in Press, published online ahead of print December 19, 2007
Mol. Biol. Cell 10.1091/mbc.E06-12-1140

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Submitted on December 21, 2006
Revised on November 26, 2007
Accepted on December 12, 2007

Inhibition of Proteasome Activity Impairs Centrosome-dependent Microtubule Nucleation and Organization

Christine Didier,* Andreas Merdes, Jean-Edouard Gairin, and Nabila Jabrane-Ferrat

L’Institut de Sciences et Technologies du Médicament de Toulouse (ISTMT), Unité Mixte de Recherche 2587 Centre National de la Recherche Scientifique-Pierre Fabre, 31400 Toulouse, France

Monitoring Editor: Yixian Zheng

Centrosomes are dynamic organelles that consist of a pair of cylindrical centrioles, surrounded by pericentriolar material. The pericentriolar material contains factors that are involved in microtubule nucleation and organization, and its recruitment varies during the cell cycle. We report here that proteasome inhibition in HeLa cells induces the accumulation of several proteins at the pericentriolar material, including gamma-tubulin, GCP4, NEDD1, ninein, pericentrin, dynactin and PCM-1. The effect of proteasome inhibition on centrosome proteins does not require intact microtubules, and is reversed after removal of proteasome inhibitors. This accrual of centrosome proteins is paralleled by accumulation of ubiquitin in the same area, and increased polyubiquitylation of nonsoluble gamma-tubulin. Cells that have accumulated centrosome proteins in response to proteasome inhibition are impaired in microtubule aster formation. Our data point toward a role of the proteasome in the turnover of centrosome proteins, to maintain proper centrosome function.

*Present address: LBCMCP, UMR5088, CNRS 118 Route de Narbonne Toulouse, 31400 France.

Address correspondence to: Nabila Jabrane-Ferrat (nabila.jabrane-ferrat{at}toulouse.inserm.fr)






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