Activity and regulation of the centrosome-associated proteasome

Regulated proteolysis is important for maintaining appropriate cellular lev els of many proteins. The bulk of intracellular protein degradation is cata lyzed by the proteasome. Recently, the centrosome was identified as a novel site for concentration of the proteasome and associated regulatory protein s (Wigley, W. C., Fabunmi, R. P., Lee, M. G., Marino, C. R., Muallem, S., D eMartino, G. N., and Thomas, P. J. (1999) J. Cell Biol. 145, 481-490). Here we provide evidence that centrosomes contain the active 26 S proteasome th at degrades ubiquitinated-protein and proteasome-specific peptide substrate s. Moreover, the centrosomes contain an ubiquitin isopeptidase activity. Th e proteolytic activity is ATP dependent and is inhibited by proteasome inhi bitors, Notably, treatment of cells with inhibitors of proteasome activity promotes redistribution of the proteasome and associated regulatory protein s to the centrosome independent of an intact microtubule system. These data provide biochemical evidence for active proteasomal complexes at the centr osome, highlighting a novel function for this organizing structure.