heat shock transcription factor-1; heat shock factor protein-1 (HSTF1, HSF1)

Function: - DNA-binding protein that specifically binds heat shock promoter elements (HSE) & activates transcription - in higher eukaryotes, HSF is unable to bind to the HSE unless the cells are heat shocked - DNA-binding homotrimer in stressed or heat shocked cells, otherwise found as a monomer - interacts with SYMPK & CSTF2 in heat-stressed cells - induced acetylation a) causes dissociation from DNA b) regulated by SIRT1 - phosphorylated on multiple Ser, a subset of which are involved in stress-related regulation of transcription activation - constitutive phosphorylation represses transcriptional activity at normal temperatures - phosphorylation on Ser-307 derepresses activation on heat-stress & in combination with Ser-303 phosphorylation appears to be involved in recovery after heat-stress - phosphorylated on Ser-230 by CAMK2, in vitro - cadmium also enhances phosphorylation on Ser-230 - phosphorylation on Ser-303 is a prerequisite for HSF1 sumoylation - phosphorylation on Ser-121 inhibits transactivation & promotes HSP90 binding - phosphorylation on Thr-142 also mediates transcriptional activity induced by heat sumoylated BY SUMO1 & SUMO₂ on heat-shock - heat-inducible sumoylation occurs after 15 min of heat-shock, after which levels decrease & at 4 hours, levels return to control levels - sumoylation has no effect on HSE binding nor on transcriptional activity - under normal conditions, interacts with HSP90AA1 in the HSP90 multichaperone complex; the interaction prevents trimerization & activation of HSF1 - on activation by heat-stress or by other factors such as metal ions, HSF1 is released from the complex, homotrimerizes, is hyperphosphorylated & translocated to the nucleus where, subsequently, it can activate transcription - binds the complex through the regulatory domain - interacts with SYMPK & CSTF2 in heat-stressed cells - interacts with FKBP4 in the HSP90 multichaperone complex; the interaction is independent of the phosphorylation state of HSF1 - interacts with MAPKAPK2 Structure: belongs to the HSF family Compartment: - cytoplasm, nucleus - cytoplasmic during normal growth & moves to the nucleus upon activation Alternative splicing: named isoforms=2

General

heat shock factor phosphoprotein

Properties

CONFIGURATION: trimer SIZE: entity length = 529 aa MW = 57 kD COMPARTMENT: cytoplasm cell nucleus MOTIF: DNA-binding motif SITE: 15-120 Hydrophobic repeat HR-A/B {130-203} Ser phosphorylation site {S303} Ser phosphorylation site {S307} Ser phosphorylation site {S314} Thr phosphorylation site {T323} Ser phosphorylation site {S326} Ser phosphorylation site {S363} HR-C {384-409}

Database Correlations

OMIM 140580 UniProt Q00613 PFAM correlations Kegg hsa:3297

References

UniProt :accession Q00613