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FLASH GENE
Symbol HSF1 contributors: mct/pgu - updated : 19-01-2015
HGNC name heat shock transcription factor 1
HGNC id 5224
Location 8q24.3      Physical location : 145.515.269 - 145.538.384
Synonym symbol(s) HSTF1
DNA
TYPE functioning gene
STRUCTURE 23.12 kb     13 Exon(s)
10 Kb 5' upstream gene genomic sequence study
motif repetitive sequence   triplet
text structure small CGG repeats in the HSF1 promoter
MAPPING cloned Y linked N status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
13 - 2166 - 529 - 1991 1871105
EXPRESSION
Type
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Visualeye   highly
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period pregnancy
Text highly expressed in oocyte
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • four leucine zipper motifs
  • two nuclear localization signals (NLS), the first reffered as HSF
  • an alpha-helix 1 in the DNA-binding domain (DBD) that stabilizes the DBD structure and facilitates the heat-induced trimerization and DNA-binding of HSF1
  • conjugated PhosphoP
    mono polymer homomer , monomer , trimer
    HOMOLOGY
    interspecies ortholog to rattus Hsf1
    ortholog to murine Hsf1
    Homologene
    FAMILY
  • HSF family
  • CATEGORY chaperone/stress , regulatory , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    intracellular,nucleus
    text
  • translocated to nucleus after heat shock activation
  • localized to the centrosome in mitosis and especially to the spindle poles in metaphase
  • normally shuttles between the nucleus and the cytoplasm, but, when activated by stressors
  • upon heat shock, HSF1 is phosphorylated, trimerizes, and translocates to the nucleus
  • basic FUNCTION
  • involved in transcriptional activation of heat shock genes
  • can activate ABCB1 expression in a stress-independent manner that differs from the canonical heat shock-activated mechanism involved in HSP induction
  • reported to induce genomic instability and aneuploidy by interaction with CDC20
  • maternal transcription factor essential for normal progression of meiosis
  • involved in several specialized cell functions (e.g. placenta formation, immunity, placode development, cancer cell viability) and is essential for female reproduction
  • plays a critical part in the regulation of oocyte meiosis and that this can be linked to its transcriptional regulation of HSP90A1, the prominent chaperone expressed in oocytes
  • playing an essential role for protecting cells from protein-damaging stress associated with misfolded proteins and regulating the insulin-signaling pathway and aging
  • required for TP53 nuclear importation and activation and implies that heat shock factors play a role in the regulation of TP53
  • required for establishment of the microtubule network in cells and for nuclear localization of TP53
  • transcription factor that plays a key role in the response to heat stress and was previously shown by us to also be essential for importation of p53 into the nucleus
  • plays an important role in checkpoint activation and DNA repair
  • required for oocyte maturation, the adult phase of meiosis preceding fertilization
  • master transcriptional regulator of the cellular response to heat and a wide variety of other stressors
  • master regulator of the heat-shock response
  • engages a regulatory program in the highly malignant state that is distinct from the classic heat-shock response
  • winged helix transcription factor that plays roles in control and stressed conditions by gaining access to target elements
  • modulates the expression of the cell survival heat shock protein 70 (HSP70) and the cell death T-cell death associated gene 51 (TDAG51) in response to heat shock and various other cell stressors
  • is induced in both cell types, epithelial cells and fibroblasts
  • critical role for HSF1 in controlling cytoprotective autophagy through regulation of ATG7, which is distinct from the HSF1 function in the heat shock response
  • CELLULAR PROCESS cell life, proliferation/growth
    cell life, cell death/apoptosis
    nucleotide, transcription, regulation
    protein, post translation, folding
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • homotrimer in stressed or heat shocked cells, otherwise found as a monomer
  • HSF1-RPA1 complex leads to preloading of RNA polymerase II and opens the chromatin structure by recruiting a histone chaperone SSRP1
  • INTERACTION
    DNA binding to heat shock element (HSE)
    RNA
    small molecule
  • Gln not only enhances the transactivation of HSF1 but also induces HSF1 expression by activating its transcription in a CEBPB-dependent manner
  • protein
  • CSTF2 in heat-stressed cells
  • SYMPK in heat-stressed cells
  • PHLDA1 is a direct target gene of HSF1
  • interacting with CGGBP1 (organizes a bifunctional transcriptional complex at small CGG repeats in the HSF1 promoter)
  • bind to the NFIX promoter and repress its expression in a heat shock sensitive manner
  • HSF1 binds avidly to the catalytic subunit of PRKACA and becomes phosphorylated on a novel serine phosphorylation site within its central regulatory domain (serine 320 or S320
  • FILIP1L interacts with HSF1, controlling its stability and thus modulating the heat shock response
  • RPA1 assists HSF1 access to nucleosomal DNA by recruiting histone chaperone FACT
  • HSF1 access to nucleosomal DNA requires its interaction with RPA1, which plays a major role in DNA replication and repair
  • PTGES3 regulates both KAT2A acetylase and HSF1 DNA binding activities
  • HSF4 occupies only CRYAB and not HSP70 promoter in epithelial cells, while HSF1 occupies only HSP70 promoter in both cell types, and CRYAB promoter, only in heat shocked fibroblasts
  • regulates autophagy by directly binding to ATG7 promoter and transcriptionally up-regulating its expression
  • promoter region of RGS2 contained a binding sequence of HSF1, which is an activator of the heat shock protein gene, and was inducibly bound by stress-activated HSF1
  • complex role for HSF1 in the regulation of ELAVL1 and CTNNB1 expression that may be significant in mammary carcinogenesis
  • direct and essential function of HSF1 in the transcriptional activation of DMRT2 and in telomere protection upon stress
  • cell & other
    REGULATION
    induced by temperature stress
    inhibited by HSP90
    Phosphorylated by MTOR (positively regulated through phosphorylation by mammalian target of rapamycin (MTOR) kinase on a key residue, serine 326, essential for transcriptional activity)
    Other inducibly acetylated at a critical residue that negatively regulates DNA binding activity
    regulated by SIRT1 (prolonged HSF1 binding to the heat shock promoter Hsp70 by maintaining HSF1 in a deacetylated, DNA-binding competent state)
    PLK1 phosphorylates HSF1 in early mitosis and the binding of phosphorylated HSF1 with CDC20 and ubiquitin degradation by SCF(beta-TrCP) regulates mitotic progression
    glutamine increases HSF1 gene transcription in a CEBPB-dependent manner and up-regulates HSF1 activity
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in prostate carcinoma
    tumoral     --over  
    in multiple myeloma
    tumoral     --over  
    is associated with reduced breast cancer survival, particularly among those with ESR1-positive disease (
    tumoral       gain of function
    in metastatic and highly tumorigenic human mammary epithelial cell lines
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • high expression of HSF1-cancer signature had a remarkable correlation with poor prognosis
  • Therapy target
    SystemTypeDisorderPubmed
    cancer  
    therapeutic role for HSF1 inhibitors in cancers
    cancerhemopathy 
    inhibition of HSF1 affects multiple protective HSPs and might therefore represent a therapeutic strategy - in particular in combination with proteasome or HSP90 inhibitors
    cancerreproductivebreast
    drugs that specifically target HSF1 function and ongoing work to develop inhibitors of HSP90 and other downstream pathways regulated by HSF1 are potential therapy in breast cancer
    ANIMAL & CELL MODELS
  • balance between the cell survival and death signals mediated by Hsp70 and Tdag51, respectively, may be disturbed by the altered expression of Hsf1 during the progression of disease in an ALS model