Chaperoning steroid hormone signaling via reversible acetylation

Abstract

Glucocorticoid receptor (GR) and related steroid hormone receptors are ligand-dependent transcription factors whose regulation is critical for both homeostasis and diseases. The structural maturation of the GR has been shown to require the Hsp90 molecular chaperone complex. Evidence indicates that Hsp90-dependent maturation is critical for GR ligand binding capacity and activity. While the role for Hsp90 in GR function is well established, the regulation of this process is not well understood. Here we discuss a recent finding that identifies reversible protein acetylation controlled by the deacetylase HDAC6 as a novel mechanism that regulates Hsp90-dependent GR maturation. We will also speculate on the implications of this finding in steroid hormone signaling, oncogenic transformation and its potential therapeutic utility.