Species Human Entrez 3297 | Human Mouse Ensembl ENSG00000185122 | |
Aliases HSF1, HSTF1, heat shock transcription factor 1 External IDs MGI: 96238 HomoloGene: 74556 GeneCards: HSF1 | ||
Heat shock factor protein 1 is a protein that in humans is encoded by the HSF1 gene.
Contents
Function
The HSF1 protein regulates the heat shock response (HSR) pathway in humans by acting as the major transcription factor for heat shock proteins. The HSR plays a protective role by ensuring proper folding and distribution of proteins within cells. This pathway is induced not only by temperature stress, but also by a variety of other stressors such as hypoxic conditions and exposure to contaminants. Hsp90, by itself and/or associated with multichaperone complexes, is a major repressor of this gene.
Mechanism of action
HSF1 exists as an inactive monomer in a complex with Hsp40/Hsp70 and Hsp90. Upon stress, such as elevated temperature, HSF1 is released from the chaperone complex and trimerizes. HSF1 is then transported into the nucleus where it is hyperphosphorylated and binds to DNA containing heat shock elements (NGAAN). HSF1's target genes include major inducible heat shock proteins such as Hsp72, and noncoding RNA within Satellite III repeat regions. Its attenuation phase is initiated as a negative feedback loop with its gene product Hsp70 binding to its transactivation domain.
Clinical significance
HSF1 is a promising drug target in cancer and proteopathy.
Interactions
HSF1 has been shown to interact with: