Fas ligand gene expression is directly regulated by stress-inducible heat shock transcription factor-1

Cell Death Differ. 2010 Jun;17(6):1034-46. doi: 10.1038/cdd.2010.4. Epub 2010 Feb 12.


Heat shock transcription factor-1 (HSF-1) is the primary stress responsive transcription factor that regulates expression of heat shock proteins (Hsps) in response to elevated temperature. We show that the transcriptional activity of HSF-1 can also directly mediate hyperthermia-induced Fas ligand (FasL) expression in activated T cells. We identify a conserved region within the human FasL promoter spanning from -276 to -236 upstream of the translational start site that contains two 15 bp non-identical adjacent HSF-1-binding sites or heat shock elements (HSEs) separated by 11 bp. Both the distal HSE (HSE1) (extending from -276 to -262) and the proximal HSE (HSE2) (spanning from -250 to -236) consist of two perfect and one imperfect nGAAn pentamers. We show the direct binding of HSF-1 to these elements and that mutation of these sites abrogates the ability of HSF-1 to bind and drive promoter activity. HSF-1 associates with these elements in a cooperative manner to mediate optimal promoter activity. We propose that the ability of HSF-1 to mediate stress-inducible expression of FasL extends its classical function as a regulator of Hsps to encompass a function for this transcription factor in the regulation of immune function and homeostasis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Cell Death
  • DNA-Binding Proteins / metabolism*
  • Fas Ligand Protein / biosynthesis
  • Fas Ligand Protein / genetics*
  • HSP70 Heat-Shock Proteins / genetics
  • Heat Shock Transcription Factors
  • Heat-Shock Response / genetics*
  • Humans
  • Jurkat Cells
  • Lymphocyte Activation
  • Promoter Regions, Genetic
  • Transcription Factors / metabolism*
  • Transcriptional Activation*


  • DNA-Binding Proteins
  • Fas Ligand Protein
  • HSF1 protein, human
  • HSP70 Heat-Shock Proteins
  • Heat Shock Transcription Factors
  • Transcription Factors