Heat shock factor

Source: Wikipedia, the free encyclopedia.
HSF-type DNA-binding
SCOP2
1hks / SCOPe / SUPFAM
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
PDB1FBQ​, 1FBS​, 1FBU​, 1FYK​, 1FYL​, 1FYM​, 1HKS​, 1HKT​, 2HTS​, 3HSF​, 3HTS​
Vertebrate heat shock transcription factor
Identifiers
SymbolVert_HS_TF
PfamPF06546
InterProIPR010542
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

In

heat shock proteins.[1][2] A typical example is the heat shock factor of Drosophila melanogaster.[3]

Function

Heat shock factors (HSF) are transcriptional activators of heat shock genes.[3] These activators bind specifically to Heat Shock sequence Elements (HSE) throughout the genome[4] whose consensus-sequence is a tandem array of three oppositely oriented "AGAAN" motifs or a degenerate version thereof. Under non-stressed conditions, Drosophila HSF is a nuclear-localized unbound monomer, whereas heat shock activation results in trimerization and binding to the HSE.[5] The Heat Shock sequence Element is highly conserved from yeast to humans.[6]

Heat shock factor 1 (HSF-1) is the major regulator of heat shock protein transcription in eukaryotes. In the absence of cellular stress, HSF-1 is inhibited by association with heat shock proteins and is therefore not active. Cellular stresses, such as increased temperature, can cause proteins in the cell to misfold. Heat shock proteins bind to the misfolded proteins and dissociate from HSF-1. This allows HSF1 to form trimers and translocate to the cell nucleus and activate transcription.[7] Its function is not only critical to overcome the proteotoxic effects of thermal stress, but also needed for proper animal development and the overall survival of cancer cells.[8][9]

Structure

Each HSF monomer contains one

nuclear localization signal (NLS). Interaction between the N- and C-terminal zippers may result in a structure that masks the NLS sequences: following activation of HSF, these may then be unmasked, resulting in relocalisation of the protein to the nucleus.[10]
The DNA-binding component of HSF lies to the N-terminus of the first NLS region, and is referred to as the HSF domain.

Isoforms

Humans express the following heat shock factors:

gene protein
HSF1 heat shock transcription factor 1
HSF2 heat shock transcription factor 2
HSF2BP heat shock transcription factor 2 binding protein
HSF4 heat shock transcription factor 4
HSF5 heat shock transcription factor family member 5
HSFX1 heat shock transcription factor family, X linked 1
HSFX2 heat shock transcription factor family, X linked 2
HSFY1 heat shock transcription factor, Y-linked 1
HSFY2 heat shock transcription factor, Y-linked 2

See also

References

  1. S2CID 5169812
    .
  2. PMID 8451637
    .
  3. ^
    S2CID 205020185
    .
  4. PMID 20844575
    .
  5. ^
    PMID 1871105
    .
  6. PMID 21467139
    .
  7. PMID 19112021
    .
  8. PMID 21576228
    .
  9. PMID 24800749
    .
  10. ^
    PMID 1871106
    .
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