Extension of the Cellular Molecular Chaperone Network

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The eukaryotic molecular chaperone network is formed by the concerted actions of Hsp90, Hsp70 and their associated cochaperones. Typically, cochaperones had been considered regulatory factors that modulate the ATPase activities of Hsp90 and Hsp70 and also guide these chaperone to distinct clients. In this study, members of the Freeman laboratory investigated the physiological pathways connected to the Hsp90 cochaperone p23 using high-throughput genomic and proteomic approaches. They focused on p23 since it is expressed in most eukaryotes, is an abundant cochaperone, forms co-complexes with unbound and client-bound Hsp90 and might also work autonomously. Their work indicates a broad p23 cellular network that includes a sizeable nuclear subnet. Empirical studies using various experimental techniques demonstrate that many of the cellular processes identified by the high-throughput assays are indeed functionally reliant on p23. Notably, a comparative bioinformatic analysis indicates that the p23 and Hsp90 networks are more distinct than anticipated. Taken together, their studies show that the p23 cochaperone serves a broad physiological client-range and functions both in conjunction with and sovereign to Hsp90. Overall, their data support a model in which cochaperones work to expand the reach of the cellular molecular chaperone network and provide a greater influence on the maintenance of homeostasis.

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Posted March 28, 2012.