Regulation of the heat shock transcriptional response: cross talk between a family of heat shock factors, molecular chaperones, and negative regulators
- Department of Biochemistry, Molecular Biology, and Cell Biology, Rice Institute for Biomedical Research, Northwestern University, Evanston, Illinois 60208 USA
This extract was created in the absence of an abstract.
Our cells and tissues are challenged constantly by exposure to extreme conditions that cause acute and chronic stress. Consequently, survival has necessitated the evolution of stress response networks to detect, monitor, and respond to environmental changes (Morimoto et al. 1990, 1994a; Baeuerle 1995; Baeuerle and Baltimore 1996; Feige et al. 1996; Morimoto and Santoro 1998). Prolonged exposure to stress interferes with efficient operations of the cell, with negative consequences on the biochemical properties of proteins that, under ideal conditions, exist in thermodynamically stable states. In stressed environments, proteins can unfold, misfold, or aggregate. Therefore, the changing demands on the quality control of protein biogenesis, challenges protein homeostasis, for which the heat shock response, through the elevated synthesis of molecular chaperones and proteases, repairs protein damage and assists in the recovery of the cell.
The inducible transcription of heat shock genes is the response to a plethora of stress signals (Lis and Wu 1993; Morimoto 1993; Wu 1995) (Fig. 1), including (1) environmental stresses, (2) nonstress conditions, and (3) pathophysiology and disease states. Although changes in heat shock protein (HSP) expression are associated with certain diseases (Morimoto et al. 1990), these observations leave open the question of whether this is an adaptation to the particular pathophysiological state, a reflection of the suboptimal cellular environment associated with the disease, or serves to warn other cells and tissues of imminent danger.
Conditions that induce the heat shock response. Heat shock gene expression represented here by the activation of HSF and binding to HSE results in the elevated expression of HSPs such as Hsp70. The regulatory conditions are represented by environmental and physiological stress and nonstressful conditions, including cell growth and development and pathophysiological states.
The protective role of HSPs is a measure of their capacity to …
