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
  • causes dissociation from DNA
  • 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

More general terms

• heat shock factor
• phosphoprotein

Database

• UniProt: http://www.uniprot.org/uniprot/Q00613.html
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:3297
• OMIM: https://mirror.omim.org/entry/140580