The DNA-binding activity of the human heat shock transcription factor is regulated in vivo by hsp70.

Abstract

The human heat shock transcription factor (HSF) is maintained in an inactive non-DNA-binding form under nonstress conditions and acquires the ability to bind specifically to the heat shock promoter element in response to elevated temperatures or other conditions that disrupt protein structure. Here we show that constitutive overexpression of the major inducible heat shock protein, hsp7O, in transfected human cells reduces the extent of HSF activation after a heat stress. HSF activation was inhibited more strongly in clones that express higher levels of hsp7O. These results demonstrate that HSF activity is negatively regulated in vivo by hsp7O and suggest that the cell might sense elevated temperature as a decreased availability of hsp7O. HSF activation in response to treatment with sodium arsenite or the proline analog azetidine was also depressed in hsp7O-expressing cells relative to that in the nontransfected control cells. As well, the level of activated HSF decreased more rapidly in the hsp7O-expressing clones when the cells were heat shocked and returned to 37°C. These results suggest that hsp7O could play an active role in the conversion of HSF back to a conformation that does not bind the heat shock promoter element during the attenuation of the heat shock response.

Heat shock transcription factor activation and Hsp72 accumulation in aged skeletal muscle

“…The exact reason (or reasons) for this differential induction of Hsp72 remains to be determined, but muscles with a high constitutive Hsp72 content before heat stress may not require the same amount of Hsp72 protein to be synthesized as muscles with a low constitutive Hsp72 content. In agreement with this are studies showing that cells overexpressing Hsp70 demonstrate a reduced HSF activation and subsequent Hsp70 accumulation when heat shocked (Baler et al 1992;Mosser et al 1993). These studies suggest a regulatory mechanism in which cells and tissues accumulate Hsp72 to a certain level, which then feeds back to shut down further Hsp72 production.…”

Firefly luciferase mutants as sensors of proteome stress

“…Adapted from (Neef et al, 2011). 3. Under normal physiological conditions, monomeric HSF1 is diffusely distributed in cytoplasm and nucleus and is kept in an inactive complex with Hsp70, Hsp40 and Hsp90 (Ali et al, 1998;Mosser et al, 1993;Nadeau et al, 1993;Zou et al, 1998). During proteotoxic stress, the structure and function of proteins is compromised, leading to the depletion of the chaperone reservoir.…”

Ha-rasval12 induces HSP70b transcription via the HSE/HSF1 system, but HSP70b expression is suppressed in Ha-rasval12-transformed cells

“…Some phosphorylations (e.g., at Ser303, Ser307) inhibit Hsf1 activity, while others (e.g., Ser320) may be involved in inducing its activity. Hsf1 seems to be also regulated by other mechanisms, including SUMO-1 modification (Hong et al, 2001), association with chaperones (Mosser et al, 1993;Baler et al, 1996;Shi et al, 1998;Zou et al, 1998), and changes of its redox state (Ahn and Thiele, 2003). Finally, as purified recombinant Hsf1 responds to heat shock in vitro (Larson et al, 1995), it seems that Hsf1 possesses intrinsic temperature sensors that make it independent of upstream signaling.…”