Salicylate Triggers Heat Shock Factor Differently than Heat

doi:10.1074/jbc.270.41.24489

Salicylate Triggers Heat Shock Factor Differently than Heat (*)

From the Section of Geriatric Medicine, Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60611

Abstract

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.

Footnotes

↵^§ Supported by Grant AG00509 from NIA, National Institutes of Health, and grants from the Buehler Center on Aging, Northwestern University, and the Veterans Administration.
↵^¶ Supported by Grant AR30692 from the National Institutes of Health.
↵* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
↵¹ The abbreviations used are:

NSAID

non-steroidal anti-inflammatory compound

HSF

heat shock transcription factor

EMSA

electromobility shift assay(s)

EMSSA

electromobility supershift assay(s)

HSE

heat shock element

PAGE

polyacrylamide gel electrophoresis.
↵²D. A. Jurivich, C. Pachetti, L. Qiu, and J. F. Welk, unpublished data.
- Received April 26, 1995.
- Revision received July 20, 1995.