Targeted Disruption of Heat Shock Transcription Factor 1 Abolishes Thermotolerance and Protection against Heat-inducible Apoptosis

TLDR

Heat shock transcription factor 1 (HSF1) regulates the synthesis of heat shock proteins, yet the distinct roles of constitutive versus inducible HSPs in mammalian thermotolerance remain unclear. Disruption of HSF1 abolishes thermotolerance and protection against heat‑induced apoptosis while leaving constitutive HSP expression unchanged, indicating that HSF1‑dependent inducible HSPs are essential for cellular adaptation to heat and that other HSFs cannot compensate.

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 in hsf1(-/-) 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.