Heat shock factor 1 (HSF1) (HSF1)

Heat shock factor 1 (HSF1) is the master transcription factor responsible for the biological process known as the heat shock response or "heat induction" of molecular chaperones (PMID: 2150530). Under basal conditions, HSF1 is primarily sequestered in an inactive monomeric state by chaperones such as HSP90 and HSP70. Upon exposure to thermal or proteotoxic stress, HSF1 is released, undergoes homotrimerization, and translocates to the nucleus where it binds to heat shock elements (HSEs) in the promoters of target genes. This activation leads to the rapid transcription of heat shock proteins (HSPs), which act as chaperones to maintain protein homeostasis and prevent apoptosis under stressful conditions (PMID: 22441905). In the context of human disease, HSF1 is a major therapeutic target in oncology because cancer cells frequently overexpress HSF1 to survive the metabolic and proteotoxic stressors of the tumor microenvironment (PMC2670238). Conversely, HSF1 activation is being explored as a strategy for treating neurodegenerative diseases, where the heat induction of chaperones can facilitate the clearance of toxic protein aggregates. Small molecule inhibitors, such as triptolide and quercetin, have been shown to interfere with HSF1-mediated transcriptional activity, effectively blocking the heat induction of cytoprotective proteins like HSP70 (PMC2670238). Recent drug development efforts focus on direct HSF1 inhibitors to overcome the specific proteotoxic dependencies of aggressive tumors.

Other names

Heat shock transcription factor 1HSTF1HSF 1

Inhibition of HSF1 trimerization, DNA binding, or phosphorylation to prevent the induction of heat shock proteins and sensitize cells to proteotoxic stress.