HDAC6-ubiquitin interaction controls the duration of HSF1 activation after heat shock.
Bottom Line: 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.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.
Affiliation: University Grenoble-Alpes, CRI INSERM, U823, Institut Albert Bonniot, La Tronche 38042, Grenoble Cedex 9, France.Show MeSH
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Mentions: To assess the role of HDAC6 in the heat-induced accumulation of HSP proteins, we examined the profile of HSP25 and HSP70 accumulation in wild-type (WT) or in HDAC6-knockout (KO) mouse 3T3 cells reexpressing or not HDAC6 bearing inactivating mutations in the two catalytic deacetylase domains (HDm) or in the ubiquitin-binding domain (Ubm; Figure 1A). Similar amounts of HDAC6 were detected by Western blot analysis in these cells, whereas acetylated tubulin (a well-known substrate of HDAC6) was only detected in HDAC6 HDm and HDAC6 KO cells (Supplemental Figure S1).
Affiliation: University Grenoble-Alpes, CRI INSERM, U823, Institut Albert Bonniot, La Tronche 38042, Grenoble Cedex 9, France.