Heat shock factor

Heat shock factor (HSF), in molecular biology, is the name given to transcription factors that regulate the expression of the heat shock proteins. A typical example is the heat shock factor of Drosophila melanogaster.

Function
Heat shock factors (HSF) are transcriptional activators of heat shock genes. They bind specifically to heat shock promoter elements, which are palindromic sequences rich with repetitive purine and pyrimidine motifs. Under normal conditions, HSF is a homo-trimeric cytoplasmic protein, but heat shock activation results in relocalisation to the nucleus.

Heat shock factor 1 (HSF-1) is the major regulator of heat shock protein transcription in eukaryotes. In the absence of cellular stress, HSF-1 is inhibited by association with heat shock proteins and is therefore not active. Cellular stresses, such as increased temperature, can cause proteins in the cell to misfold. Heat shock proteins bind to the misfolded proteins and dissociate from HSF-1. This allows HSF1 to form trimers and translocate to the cell nucleus and activate transcription.

Structure
Each HSF monomer contains one C-terminal and three N-terminal leucine zipper repeats. Point mutations in these regions result in disruption of cellular localisation, rendering the protein constitutively nuclear. Two sequences flanking the N-terminal zippers fit the consensus of a bi-partite nuclear localization signal (NLS). Interaction between the N- and C-terminal zippers may result in a structure that masks the NLS sequences: following activation of HSF, these may then be unmasked, resulting in relocalisation of the protein to the nucleus. The DNA-binding component of HSF lies to the N-terminus of the first NLS region, and is referred to as the HSF domain.

Isoforms
Humans express the following heat shock factors: