BIOLOGICAL ROLES OF VARIOUS STRESS PROTEINS AND THEIR CLINICAL IMPLICATIONS

All living cells, from the simplest prokaryote to the most complex multicellular organism, contain stress proteins-molecular chaperones that are responsible for management of unfolded polypeptides within the cell. Unfolded polypeptides are generated during protein synthesis, and also as a result of breakdown associated with protein turnover. Interaction of polypeptides with the chaperone proteins plays an essential role in their folding and assembly into functionally mature oligomers and regulates trafficking between intracellular compartments. Particularly high levels of molecular chaperones are required to maintain protein homeostasis in cells subjected to stress conditions-such as heat shock, nutrient deprivation, malignant transformation, and anoxia-when intracellular proteins are destabilized, or when a major alteration is required in overall cell protein composition. In view of the fundamental role of stress proteins in maintenance of protein homeostasis, it seems likely that malfunctions associated with members of stress protein families would have pathological effects. Such effects might be minimal under normal physiological conditions, but could be exacerbated at times. This review provides an overview of the cell biology and immunology of stress proteins focusing predominantly on immunological responses to stress proteins in a range of immune-mediated diseases and in infectious diseases.