HSF1 Gene: Master Regulator of the Heat Shock Response and Proteostasis
Explore the HSF1 gene, its protein product, genomic context, expression patterns, disease associations, and functional roles in stress response and cancer.
Gene Information Card
| Symbol | HSF1 |
|---|---|
| Full Name | Heat Shock Transcription Factor 1 |
| Gene Type | protein coding |
| Chromosomal Location | 8q24.3 |
| NCBI Gene ID | 3297 ncbi.nlm.nih.gov/gene/3297 |
| Ensembl ID | ENSG00000185122 |
| UniProt ID | Q00613 |
| OMIM ID | 140580 |
| HGNC ID | 5224 |
| Aliases | HSTF1, heat shock factor protein 1 |
Description
The HSF1 gene encodes heat shock transcription factor 1, a master regulator of the heat shock response. HSF1 is a stress-inducible transcription factor that binds to heat shock elements (HSEs) in the promoters of target genes, including heat shock proteins (HSPs), to promote their expression under proteotoxic stress. Beyond the classical heat shock response, HSF1 is involved in development, metabolism, and tumorigenesis. It is a key mediator of cellular proteostasis and is implicated in various diseases, including cancer and neurodegenerative disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | HSF1 promotes tumorigenesis by supporting proteostasis, metabolic reprogramming, and stress resistance in cancer cells. It is overexpressed or hyperactivated in many tumors. | COSMIC; multiple studies (e.g., Mendillo et al., 2012, Cell) |
| Neurodegenerative diseases (e.g., Alzheimer's, Parkinson's, Huntington's) | HSF1-mediated heat shock response is impaired, leading to protein misfolding and aggregation. Enhancing HSF1 activity is protective in models. | OMIM; PubMed (e.g., Neef et al., 2011, Nat Rev Drug Discov) |
| Proteostasis disorders (e.g., protein aggregation diseases) | Loss of HSF1 function reduces HSP expression, exacerbating protein aggregation and cellular toxicity. | OMIM; PubMed (e.g., Anckar & Sistonen, 2011, Annu Rev Biochem) |
| Inherited HSF1-related disorders (rare) | Mutations in HSF1 are rare; some variants may affect stress response and are linked to susceptibility to environmental stressors. | ClinVar (limited entries) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 10.2 | Medium |
| Kidney | 8.5 | Medium |
| Liver | 7.8 | Medium |
| Brain | 6.4 | Low |
| Heart | 5.9 | Low |
| Lung | 5.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical cancer) | 12.3 | High expression; used in stress response studies |
| HepG2 (liver cancer) | 9.8 | Moderate expression |
| A549 (lung cancer) | 8.1 | Moderate expression |
| MCF7 (breast cancer) | 7.5 | Low-moderate expression |
| K562 (leukemia) | 6.9 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1Val) | Missense | Rare | Potential loss of function; affects translation initiation |
| c.104C>T (p.Pro35Leu) | Missense | Rare | May affect DNA-binding domain; functional impact unknown |
| c.125G>A (p.Arg42His) | Missense | Rare | In DNA-binding domain; possibly affects HSE binding |
| c.463C>T (p.Arg155Cys) | Missense | Rare | In trimerization domain; may disrupt oligomerization |
| c.1000G>A (p.Val334Ile) | Missense | Rare | In regulatory domain; potential effect on activation |
Mutation functional classification
Loss of Function (LOF)
Rare missense mutations in the DNA-binding or trimerization domains may impair HSF1's ability to bind DNA or form active trimers, reducing target gene expression and compromising the heat shock response.
Gain of Function (GOF)
No clear gain-of-function mutations have been reported. However, overexpression or hyperactivation of wild-type HSF1 is common in cancers, contributing to oncogenic phenotypes.
Dominant Negative (DN)
Mutations that disrupt trimerization could act in a dominant-negative manner, interfering with wild-type HSF1 function, though such variants are not well-documented in ClinVar.
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity | • RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| • heat shock protein binding | • protein homodimerization activity |
| • protein heterodimerization activity | • transcription cis-regulatory region binding |
| • chromatin binding | • ubiquitin protein ligase binding |
| • response to heat | • cellular response to stress |
| • regulation of transcription by RNA polymerase II | • positive regulation of transcription by RNA polymerase II |
| • negative regulation of transcription by RNA polymerase II | • protein folding |
| • chaperone cofactor-dependent protein refolding | • cellular response to unfolded protein |
| • regulation of cell population proliferation | • apoptotic process |
| • aging | • circadian rhythm |
Pathways
• Heat shock response pathway
• Cellular response to heat stress
• Proteostasis network
• Regulation of HSF1-mediated heat shock response
• Protein processing in endoplasmic reticulum
• MAPK signaling pathway (regulation of HSF1)
• PI3K-Akt signaling pathway (cross-talk)
• p53 signaling pathway (interaction)
Protein Summary
HSF1 is a 529-amino acid transcription factor that contains an N-terminal DNA-binding domain, a trimerization domain (leucine zipper), a regulatory domain, and a C-terminal activation domain. Under normal conditions, HSF1 is monomeric and inactive, bound by chaperones such as Hsp90. Upon stress (e.g., heat shock, oxidative stress, proteotoxic insults), HSF1 trimerizes, translocates to the nucleus, and binds to heat shock elements (HSEs) in target gene promoters, activating transcription of HSPs and other stress-responsive genes. HSF1 also regulates genes involved in metabolism, cell cycle, and apoptosis. Its activity is modulated by post-translational modifications including phosphorylation, sumoylation, and acetylation. In cancer, HSF1 supports malignant transformation and metastasis by maintaining proteostasis and promoting metabolic adaptations.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HSF1 Knockout HEK293 Cell Line | EDJ-KQ2574 | Human | 3297 | Details Get a Quote |
| HSF1 Knockout HCT 116 Cell Line | EDJ-KQ24640 | Human | 3297 | Details Get a Quote |
| HSF1 Knockout HeLa Cell Line | EDJ-KQ24641 | Human | 3297 | Details Get a Quote |
| HSF1 Knockout A-549 Cell Line | EDJ-KQ62045 | Human | 3297 | Details Get a Quote |
