SALICYLATE TRIGGERS HEAT-SHOCK FACTOR DIFFERENTLY THAN HEAT

Sodium salicylate has the unusual property of partially inducing the h uman heat shock response (Jurivich, D. A., Sistonen, L., Kroes, R., an d Morimoto, R.I. (1992) Science 255, 1243-1245). Salicylate induces th e DNA binding state of the human heat shock transcription factor (HSF) , but this is insufficient to elevate heat shock gene expression. Beca use it is not known how HSF enhances heat shock gene expression, furth er analysis of the transcriptionally inert, salicylate-induced HSF was undertaken to potentially identify components of the heat shock respo nse that are necessary for full transcriptional induction. Like therma l stress, exposure of HeLa cells to salicylate led to the induction of HSF1 into a DNA-bound state. Despite continued exposure of cells to s alicylate, HSF1 DNA binding attenuated much more rapidly than a contin uous heat shock. Western blot analysis revealed that the salicylate-in duced form of HSF1 was not hyperphosphorylated like the heat-induced f orm. Furthermore, supershifts of the HSF1 bound to an heat shock eleme nt (HSE) oligonucleotide by monoclonal antibodies to phosphoamino acid s revealed that salicylate induced threonine phosphorylation of HSF1, whereas heat led to a predominance of HSF1 serine phosphorylation. The se data suggest that salicylate-independent signals are necessary to c onvert HSF1 into a transactivator of heat shock gene expression and th at brief acquisition of DNA binding by this factor is insufficient to maximally enhance transcription.