Stress-Induced Expression of Heat Shock Proteins and Action of the Heat Shock Protein Effectors

Abstract

The heat shock response is a universal cellular response to stressful conditions, including not only heat exposure but also exposure to a variety of other noxious agents and conditions including oxidants, heavy metals, pH change, and nutrient starvation. In all cases, cells sense the stressful condition and respond by inducing the expression of a set of genes encoding so-called heat shock proteins (Hsps). Sensing, as reviewed below, appears in general to involve the recognition of misfolding proteins, as an immediate by-product of the stress conditions. Thus, there is a fairly uniform response mediated to the variety of different stresses. The induced heat shock proteins, whose structure and action is also reviewed here, include molecular chaperones and proteases, which act as agents that serve to protect the cell against the imposed stress. The chaperones act to stabilize misfolding proteins and assist them back to native form while in the case of proteases the action is to remove misfolded proteins by degradation. Notably, whereas such components were identified originally by their induction during stress, many of them have been subsequently observed to mediate the same actions, in many cases essential, under normal conditions. Included also in the stress-responding armamentarium are a number of components that bind to or modify nucleic acids and, while such components are at an earlier stage of study, these also may confer protection on nucleic acid containing machines such as chromatin and the ribosome.

The heat shock response can thus be conveniently considered as a “sensing” circuitry that mounts a transcriptional response to imposed stress, and an “effector” arm consisting of a variety of actions mediated by the heat shock proteins. We consider first the sensing system in bacteria and then eukaryotes, and then review the structure and action of the effectors.