Aged HSF1 muscle-specific knockout mice show deteriorated muscle atrophy and metabolic dysfunction, while active HSF1 overexpression improves muscle function via activating SIRT3 to deacetylate both ...

Heat shock factor 1 (HSF1) is the master transcriptional regulator of cellular response to disrupted cytosolic protein homeostasis. Temperature change, oxidation, and other stresses drive the trimeriz...

Increased activity of heat shock factor 1 (HSF1) promotes longevity; however, the mechanisms underlying this are unclear. Here, the authors show that in the nematode worm Caenorhabditis elegans, HSF1 ...

The nuclear J-domain protein Apj1 controls the shut-off phase of the yeast heat shock response by displacing DNA-bound heat shock transcription factor Hsf1.

Konada et al. report that heat shock factor 1 (HSF1) selectively stimulates the topoisomerase II (TOP2) isoform, TOP2B, over TOP2A, in both dividing cells and postmitotic neurons. Employing HSF1 inhibitors could blunt the secondary toxicity of TOP2 poison-based chemotherapy toward postmitotic cells without compromising their ability to kill cancer cells.

Abstract. Transcription factor heat shock factor 1 (HSF1) orchestrates the cellular stress response, promoting malignant transformation, unchecked prolifer

The degeneration of neurons in patients with amyotrophic lateral sclerosis (ALS) is commonly associa

Konada et al. report that heat shock factor 1 (HSF1) selectively stimulates the topoisomerase II (TOP2) isoform, TOP2B, over TOP2A, in both dividing cells and postmitotic neurons. Employing HSF1 inhibitors could blunt the secondary toxicity of TOP2 poison-based chemotherapy toward postmitotic cells without compromising their ability to kill cancer cells.

The nuclear J-domain protein Apj1 controls the shut-off phase of the yeast heat shock response by displacing DNA-bound heat shock transcription factor Hsf1.

Proteasome inhibitors have proven highly effective in multiple myeloma but not in acute myeloid leukemia. The addition of a drug that inactivates the HSF1 pathway or impairs autophagy could change…

Heat shock factor 1 (HSF1) is the critical orchestrator of cell responses to heat shock, and its dysfunction is linked to various diseases. HSF1 undergoes phase separation upon heat shock, and its activity is regulated by post-translational modifications (PTMs). The molecular details underlying HSF1 phase separation, temperature sensing and PTM regulation remain poorly understood. Here, we discovered that HSF1 exhibits temperature-dependent phase separation with a lower critical solution temperature behavior, providing a new conceptual mechanism accounting for HSF1 activation. We revealed the residue-level molecular details of the interactions driving the phase separation of wild-type HSF1 and its distinct PTM patterns at various temperatures. The mapped interfaces were validated experimentally and accounted for the reported HSF1 functions. Importantly, the molecular grammar of temperature-dependent HSF1 phase separation is species specific and physiologically relevant. These findings

Ren et al. find that HSF1 undergoes lower critical solution temperature type phase separation, correlating with species’ physiological temperatures, which is driven by the regulatory domain in its int...

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