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: In conclusion, our data reveal that p97/VCP is not critical for HSF1 activation in heat-shocked cells but plays an important role in the reformation of the inactive HSF1 complex. We found that VCP accelerates the reformation of the repressive HSF1 complex when binding of HDAC6 to ubiquitinated residues no longer occurs (Figure 5).
Affiliation: University Grenoble-Alpes, CRI INSERM, U823, Institut Albert Bonniot, La Tronche 38042, Grenoble Cedex 9, France.