[4] HSF1 is highly conserved in eukaryotes and is the primary mediator of transcriptional responses to proteotoxic stress with important roles in non-stress regulation such as development and metabolism.

This N-terminal domain of approximately 100 amino acids is the most highly conserved region in the HSF protein family and consists of a helix-turn-helix loop.

Repeated sequences of the nGAAn pentamer constitute heat shock elements (HSEs) for active HSF1 trimers to bind.

[7] HSF1 transactivates genes for many cytoprotective proteins involved in heat shock, DNA damage repair, and metabolism.

[7][9] In the event of proteotoxic stress such as heat shock, these chaperones are released from HSF1 to perform their protein-folding roles; simultaneously, the export of HSF1 to the cytoplasm is inhibited.

The ability of cancer cells to use HSF1 in a unique manner gives this protein significant clinical implications for therapies and prognoses.

In recent years, using cells that express the poly-glutamine expansion found in HD, it has been shown that both the HSR and HSF1 levels are reduced after heat shock.