HDAC6-ubiquitin interaction controls the duration of HSF1 activation after heat shock.

After heat shock, HSF1 controls a major cellular transcriptional response involving the activation of early (HSP70) and late (HSP25) heat shock gene expression. Here we show that a full response to heat shock (activation of both HSP70 and HSP25) depends on the duration of HSF1 activation, which is itself controlled by HDAC6, a unique deacetylase known to bind monoubiquitin and polyubiquitin with high affinity. On the basis of a comparative analysis of the heat shock response in cells knocked out for HDAC6 or expressing HDAC6 mutants, we show that HDAC6 binding to ubiquitinated proteins controls the duration of HSF1 activation after heat shock. In cells expressing HDAC6 mutated in the ubiquitin-binding domain, the AAA ATPase factor p97/VCP mediates rapid inactivation of HSF1, precluding late activation of the HSP25 gene. In these cells, knockdown of p97/VCP rescues HSF1 from this rapid inactivation and restores HSP25 expression. We present here a new regulatory circuit that adjusts the duration of the heat shock response to the extent of protein ubiquitination after heat shock.
AuthorsLydia Pernet, Virginie Faure, Benoit Gilquin, Solenne Dufour-Guérin, Saadi Khochbin, Claire Vourc'h
JournalMolecular biology of the cell (Mol Biol Cell) Vol. 25 Issue 25 Pg. 4187-94 (Dec 15 2014) ISSN: 1939-4586 [Electronic] United States
PMID25298398 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2014 Pernet, Faure, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).
Chemical References
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Heat-Shock Proteins
  • Hsf1 protein, mouse
  • Hspb1 protein, mouse
  • Neoplasm Proteins
  • Transcription Factors
  • Ubiquitin
  • Hdac6 protein, mouse
  • Histone Deacetylases
  • Adenosine Triphosphatases
  • CDC48 protein
  • 3T3 Cells
  • Adenosine Triphosphatases (metabolism)
  • Animals
  • Cell Cycle Proteins (metabolism)
  • DNA-Binding Proteins (metabolism)
  • Gene Expression Regulation
  • Heat-Shock Proteins (metabolism)
  • Heat-Shock Response
  • Histone Deacetylases (physiology)
  • Mice
  • Neoplasm Proteins (metabolism)
  • Promoter Regions, Genetic
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Transcription Factors (metabolism)
  • Ubiquitin (metabolism)
  • Ubiquitination

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