The Centrosome and its Functions and Dysfunctions

Schatten, Heide

Among the multiple and intriguing roles of centrosomes in cellular functions is the ubiquitin-proteasome-mediated protein degradation. It has been shown that proteasomes are concentrated at the mammalian centrosome which led to further studies to view the centrosome as a proteolytic center (Wojcik et al. 1996; Wigley et al. 1999; reviewed in Badano et al. 2005). Proteasomal components that are concentrated around the centrosome include ubiquitin, the 20S and 19S subunits of the proteasome, as well as the E3 enzyme parkin. These proteasomal components colocalize with the centrosomal marker γ-tubulin and co-purify with γ-tubulin in the centrosomal fractions after sucrose-gradient ultracentrifugation (Wigley et al. 1999). The localization, accumulation, and concentration of proteasomal components around centrosomes appear to be microtubule independent which has been shown experimentally by inhibiting microtubule functions. When intracellular levels of misfolded proteins were experimentally increased by either proteasome inhibition with drugs such as lactacystin, or by overexpression of misfolded mutant proteins, the centrosome-associated proteasome network became expanded and proteolytic components were recruited from the cytosol without involvement of microtubules. These studies revealed a critical role of centrosomes in the organization and subcellular localization of proteasomes (Wigley et al. 1999; Fabunmi et al. 2000).