Requirement of Hsp90 for centrosomal function reflects its regulation of Polo kinase stability

Abstract

We have previously shown that the molecular chaperone heat shock protein 90 (Hsp90) is required to ensure proper centrosome function in Drosophila and vertebrate cells. This observation led to the hypothesis that this chaperone could be required for the stability of one or more centrosomal proteins. We have found that one of these is Polo, a protein kinase known to regulate several aspects of cell division including centrosome maturation and function. Inhibition of Hsp90 results in the inactivation of Polo kinase activity. It also leads to a loss in the ability of cytoplasmic extracts to complement the failure of salt-stripped preparations of centrosomes to nucleate microtubules. This effect can be rescued upon addition of active recombinant Polo. We also show that Polo and Hsp90 are part of a complex and conclude that stabilization of Polo is one of the mechanisms by which Hsp90 contributes to the maintenance of functional centrosomes.

Regulation of Greatwall kinase by protein stabilization and nuclear localization

“…[22][23][24][25] It has been shown that the evolutionarily conserved protein association between Plk1 and Hsp90 was required for the stability of Plk1, and thereby involved in centrosomal functions and metaphaseto-anaphase transition. 22,26 In this study we discovered Hsp90 as a major associated partner for Gwl. Further analysis showed that the N-terminal segment of Gwl mediated its association with Hsp90.…”

Yeast polo-like kinases: functionally conserved multitask mitotic regulators

“…Loss of fission yeast Plo1 function leads to a mitotic arrest in which condensed chromosomes are associated with a monopolar spindle (Ohkura et al, 1995). In addition, microtubule nucleation activity of the salt-stripped Drosophila centrosomes can be rescued upon addition of active recombinant Polo (De Carcer et al, 2001). These findings suggest that one of the most critical functions of Plks is to regulate bipolar spindle formation.…”

Arsenite-induced mitotic death involves stress response and is independent of tubulin polymerization

“…Lack of statistical significance could be due to the presence of constitutive HSP70, HSP90, and other constitutive or inducible HSP and HSP-like proteins capable of protecting the cell from arsenite treatment. Both HSP90 and HSP70 are located at and help regulate the centrosome during mitosis (Rattner, 1991;de Carcer et al, 2001). HSP70 and HSP90 work cooperatively in a complex (Schumacher et al, 1996;Hernandez et al, 2002).…”