Inhibition of proteasome activity impairs centrosome-dependent microtubule nucleation and organization.
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.
Didier
Christine
C
Institut de Sciences et Technologies du Médicament de Toulouse, Unité Mixte de Recherche 2587 Centre National de la Recherche Scientifique-Pierre Fabre, 31400 Toulouse, France.
Merdes
Andreas
A
Gairin
Jean-Edouard
JE
Jabrane-Ferrat
Nabila
N
D002460:Cell Line; D002502:Centrioles / Q000187:drug effects / Q000378:metabolism; D018385:Centrosome / Q000378:metabolism* / Q000648:ultrastructure; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D053141:Organelle Size / Q000187:drug effects; D061988:Proteasome Inhibitors; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D012995:Solubility / Q000187:drug effects; D014404:Tubulin / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism
D002868:Chromosomal Proteins, Non-Histone; D004791:Enzyme Inhibitors; D061988:Proteasome Inhibitors; D014404:Tubulin; D025801:Ubiquitin