Targeted Disruption of Heat Shock Transcription Factor 1 Abolishes Thermotolerance and Protection against Heat-inducible Apoptosis*
- From the Departments of ‡Internal Medicine and§Biochemistry, Molecular Cardiology Research Laboratories, The University of Texas Southwestern Medical Center, Dallas, Texas 75235-8573
Abstract
Heat shock transcription factor 1 (HSF1) is a member of the vertebrate HSF family that regulates stress-inducible synthesis of heat shock proteins (HSPs). Although the synthesis of the constitutively expressed and inducible members of the heat shock family of stress proteins correlates with increased cellular protection, their relative contributions in acquired cellular resistance or “thermotolerance” in mammalian cells is presently unknown. We report here that constitutive expression of multiple HSPs in cultured embryonic cells was unaffected by disruption of the murine HSF1 gene. In contrast, thermotolerance was not attainable inhsf1 (−/−) cells, and this response was required for protection against heat-induced apoptosis. We conclude that 1) constitutive and inducibly expressed HSPs exhibit distinct physiological functions for cellular maintenance and adaptation, respectively, and 2) other mammalian HSFs or distinct evolutionarily conserved stress response pathways do not compensate for HSF1 in the physiological response to heat shock.
Footnotes
-
↵* The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
-
↵¶ Recipient of the National Institutes of Health (K14) Career Development and Established Investigator Award of the American Heart Association. To whom correspondence and reprint requests should be addressed: Molecular Cardiology Research Laboratories, University of Texas Southwestern Medical Center, Dallas, TX 75235-8573. Tel.: 214-648-1423; Fax: 214-648-1475; E-mail:benjamin{at}ryburn.swmed.edu.
-
↵1 The abbreviations used are: HSF, heat shock transcription factor; HSE, heat shock element; HSP (and Hsp), heat shock protein; GRP78/BiP, immunoglobulin heavy chain binding protein/78-kDa glucose-regulated protein; kb, kilobase pair(s); PC, preconditioned; LS, lethal heat stress; TUNEL, terminal deoxynucleotidyltransferase dUTP nick end labeling.
-
↵2 X. Xiao and I. J. Benjamin, unpublished results.
-
↵3 X. Xiao and I. J. Benjamin, manuscript in preparation.
-
↵4 X. Xiao and I. J. Benjamin, unpublished results.
-
↵5 A. A. Davis, X. Xiao, and I. J. Benjamin, work in progress.
-
- Received November 3, 1997.
- The American Society for Biochemistry and Molecular Biology, Inc.
