Salicylate triggers heat shock factor differently than heat.
Sodium salicylate has the unusual property of partially inducing the human heat shock response (Jurivich, D. A., Sistonen, L., Kroes, R., and Morimoto, R. I. (1992) Science 255, 1243-1245). Salicylate induces the DNA binding state of the human heat shock transcription factor (HSF), but this is insufficient to elevate heat shock gene expression. Because it is not known how HSF enhances heat shock gene expression, further analysis of the transcriptionally inert, salicylate-induced HSF was undertaken to potentially identify components of the heat shock response that are necessary for full transcriptional induction. Like thermal stress, exposure of HeLa cells to salicylate led to the induction of HSF1 into a DNA-bound state. Despite continued exposure of cells to salicylate, HSF1.DNA binding attenuated much more rapidly than a continuous heat shock. Western blot analysis revealed that the salicylate-induced form of HSF1 was not hyperphosphorylated like the heat-induced form. Furthermore, supershifts of the HSF1 bound to an heat shock element (HSE) oligonucleotide by monoclonal antibodies to phosphoamino acids revealed that salicylate induced threonine phosphorylation of HSF1, whereas heat led to a predominance of HSF1 serine phosphorylation. These data suggest that salicylate-independent signals are necessary to convert HSF1 into a transactivator of heat shock gene expression and that brief acquisition of DNA binding by this factor is insufficient to maximally enhance transcription.
Jurivich
D A
DA
Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Pachetti
C
C
Qiu
L
L
Welk
J F
JF
D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism; D002846:Chromatography, Affinity; D002848:Chromatography, DEAE-Cellulose; D004273:DNA, Neoplasm / Q000302:isolation & purification / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D015870:Gene Expression / Q000187:drug effects; D006367:HeLa Cells; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000302:isolation & purification; D006358:Hot Temperature; D006801:Humans; D007700:Kinetics; D010766:Phosphorylation; D011485:Protein Binding; D012980:Sodium Salicylate / Q000494:pharmacology*; D014157:Transcription Factors / Q000096:biosynthesis / Q000378:metabolism*; D014158:Transcription, Genetic
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; D014157:Transcription Factors; D012980:Sodium Salicylate