Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

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

Molecular cell | May 27, 2005

http://www.ncbi.nlm.nih.gov/pubmed/15916966

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.

Pubmed ID: 15916966 RIS Download

Mesh terms: Acetylation | Animals | Cell Line | Dexamethasone | Glucocorticoids | HSP90 Heat-Shock Proteins | Histone Deacetylases | Humans | Mice | Receptors, Glucocorticoid | Signal Transduction | Transcription, Genetic

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NCI NIH HHS, Id: CA28010
  • Agency: NIDDK NIH HHS, Id: DK31573

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.