HDAC6 controls major cell response pathways to cytotoxic accumulation of protein aggregates.

Journal Article (Journal Article)

A cellular defense mechanism counteracts the deleterious effects of misfolded protein accumulation by eliciting a stress response. The cytoplasmic deacetylase HDAC6 (histone deacetylase 6) was previously shown to be a key element in this response by coordinating the clearance of protein aggregates through aggresome formation and their autophagic degradation. Here, for the first time, we demonstrate that HDAC6 is involved in another crucial cell response to the accumulation of ubiquitinated protein aggregates, and unravel its molecular basis. Indeed, our data show that HDAC6 senses ubiquitinated cellular aggregates and consequently induces the expression of major cellular chaperones by triggering the dissociation of a repressive HDAC6/HSF1 (heat-shock factor 1)/HSP90 (heat-shock protein 90) complex and a subsequent HSF1 activation. HDAC6 therefore appears as a master regulator of the cell protective response to cytotoxic protein aggregate formation.

Full Text

Duke Authors

Cited Authors

  • Boyault, C; Zhang, Y; Fritah, S; Caron, C; Gilquin, B; Kwon, SH; Garrido, C; Yao, T-P; Vourc'h, C; Matthias, P; Khochbin, S

Published Date

  • September 1, 2007

Published In

Volume / Issue

  • 21 / 17

Start / End Page

  • 2172 - 2181

PubMed ID

  • 17785525

Pubmed Central ID

  • PMC1950856

International Standard Serial Number (ISSN)

  • 0890-9369

Digital Object Identifier (DOI)

  • 10.1101/gad.436407


  • eng

Conference Location

  • United States