HDAC6 regulates Hsp90 acetylation and chaperone-dependent activation of glucocorticoid receptor.

Published

Journal Article

The molecular chaperone heat shock protein 90 (Hsp90) and its accessory cochaperones function by facilitating the structural maturation and complex assembly of client proteins, including steroid hormone receptors and selected kinases. By promoting the activity and stability of these signaling proteins, Hsp90 has emerged as a critical modulator in cell signaling. Here, we present evidence that Hsp90 chaperone activity is regulated by reversible acetylation and controlled by the deacetylase HDAC6. We show that HDAC6 functions as an Hsp90 deacetylase. Inactivation of HDAC6 leads to Hsp90 hyperacetylation, its dissociation from an essential cochaperone, p23, and a loss of chaperone activity. In HDAC6-deficient cells, Hsp90-dependent maturation of the glucocorticoid receptor (GR) is compromised, resulting in GR defective in ligand binding, nuclear translocation, and transcriptional activation. Our results identify Hsp90 as a target of HDAC6 and suggest reversible acetylation as a unique mechanism that regulates Hsp90 chaperone complex activity.

Full Text

Duke Authors

Cited Authors

  • Kovacs, JJ; Murphy, PJM; Gaillard, S; Zhao, X; Wu, J-T; Nicchitta, CV; Yoshida, M; Toft, DO; Pratt, WB; Yao, T-P

Published Date

  • May 27, 2005

Published In

Volume / Issue

  • 18 / 5

Start / End Page

  • 601 - 607

PubMed ID

  • 15916966

Pubmed Central ID

  • 15916966

International Standard Serial Number (ISSN)

  • 1097-2765

Digital Object Identifier (DOI)

  • 10.1016/j.molcel.2005.04.021

Language

  • eng

Conference Location

  • United States