title: HDAC6-ubiquitin interaction controls the duration of HSF1 activation after heat shock.
abstract: 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.
authors.affiliation: University Grenoble-Alpes, CRI INSERM, U823, Institut Albert Bonniot, La Tronche 38042, Grenoble Cedex 9, France.
authors.forename: Lydia
authors.initials: L
authors.lastname: Pernet
authors.affiliation: University Grenoble-Alpes, CRI INSERM, U823, Institut Albert Bonniot, La Tronche 38042, Grenoble Cedex 9, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Faure
authors.affiliation: University Grenoble-Alpes, CRI INSERM, U823, Institut Albert Bonniot, La Tronche 38042, Grenoble Cedex 9, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Gilquin
authors.affiliation: University Grenoble-Alpes, CRI INSERM, U823, Institut Albert Bonniot, La Tronche 38042, Grenoble Cedex 9, France.
authors.forename: Solenne
authors.initials: S
authors.lastname: Dufour-Guérin
authors.affiliation: University Grenoble-Alpes, CRI INSERM, U823, Institut Albert Bonniot, La Tronche 38042, Grenoble Cedex 9, France claire.vourch@ujf-grenoble.fr saadi.khochbin@ujf-grenoble.fr.
authors.forename: Saadi
authors.initials: S
authors.lastname: Khochbin
authors.affiliation: University Grenoble-Alpes, CRI INSERM, U823, Institut Albert Bonniot, La Tronche 38042, Grenoble Cedex 9, France claire.vourch@ujf-grenoble.fr saadi.khochbin@ujf-grenoble.fr.
authors.forename: Claire
authors.initials: C
authors.lastname: Vourc'h
mesh_terms: D016475:3T3 Cells; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000378:metabolism; D018869:Heat-Shock Response; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000502:physiology*; D051379:Mice; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D014157:Transcription Factors / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*; D054875:Ubiquitination; D000074405:Valosin Containing Protein
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; C486113:Hsbp1 protein, mouse; C490017:Hsf1 protein, mouse; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D014157:Transcription Factors; D025801:Ubiquitin; C499033:Hdac6 protein, mouse; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases; D000251:Adenosine Triphosphatases; D000074405:Valosin Containing Protein; C000614179:Vcp protein, mouse