Post-translational modifications of Hsp90 and their contributions to chaperone regulation - PubMed (original) (raw)

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Post-translational modifications of Hsp90 and their contributions to chaperone regulation

Mehdi Mollapour et al. Biochim Biophys Acta. 2012 Mar.

Abstract

Molecular chaperones, as the name suggests, are involved in folding, maintenance, intracellular transport, and degradation of proteins as well as in facilitating cell signaling. Heat shock protein 90 (Hsp90) is an essential eukaryotic molecular chaperone that carries out these processes in normal and cancer cells. Hsp90 function in vivo is coupled to its ability to hydrolyze ATP and this can be regulated by co-chaperones and post-translational modifications. In this review, we explore the varied roles of known post-translational modifications of cytosolic and nuclear Hsp90 (phosphorylation, acetylation, S-nitrosylation, oxidation and ubiquitination) in fine-tuning chaperone function in eukaryotes. This article is part of a Special Issue entitled: Heat Shock Protein 90 (HSP90).

Published by Elsevier B.V.

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Figures

Figure 1

Figure 1

Post-translational modification of Hsp90 fine-tunes its chaperone function. ATP binding to the N-terminal domain of Hsp90 (gray) promotes transient dimerization of the N-domains (closed conformation). Subsequent structural rearrangements establish the ’closed and twisted’ conformation capable of ATP hydrolysis. The co-chaperone Aha1 enhances Hsp90 ATPase activity by facilitating the conformational changes necessary to achieve ATPase competence, while Sti1 and Hsp90 inhibitors such as geldanamycin (GA) or radicicol (RD) exert the opposite effect by inhibiting the initial structural changes necessary for N-domain dimerization. p23 slows ATP hydrolysis at a late stage of the chaperone cycle. Domain labeling is as follows: N, N-domain (gray); CL, charged linker (yellow); M, M-domain (amber); C, C-domain (green).

Figure 2

Figure 2

Post-translational modification sites on Hsp90. Domain location of phosphorylated serine (S), theronine (T) and tyrosine (Y) sites for which kinases are known, acetylated lysine (K) residues (pale blue), S-nitrosylated cysteine (C) (green) and cysteine oxidation sites (brown) on human Hsp90α and Hsp90β are shown. For additional phosphorylation sites, the reader is referred to [64,76].

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