The Ubiquitin System and the Heat Shock Response

Abstract

A cell subjected to an increase in temperature as little as 10% above the physiologically normal range suffers damage that can permanently affect its growth and function. There are, however, a number of activities that protect the cell from a heat shock as well as other kinds of environmental stress. Research over the past 15 years has clearly established that one of these protective mechanisms is the induction of heat shock proteins. Chapters in this volume provide important clues as to how the synthesis of the major universal stress protein HSP70 is regulated and how it functions as a “ehaperone” to form complexes with proteins that misfold or unfold during stress and thus “rescue” these proteins from irreversible damage and degradation. Two recent reviews (Pelham 1989; Rothman 1989) elaborate further on functions of several proteins closely related in structure to the major heat shock proteins. But not all stress-damaged proteins can be rescued and it is now clear that stressed cells also activate several components of a proteolytic degradation system that normally functions to “turn over” cytoplasmic and nuclear proteins. This enzymatic pathway is found in all eukaryotic cells and employs the small polypeptide called ubiquitin to mark a protein for proteolysis. Many of the enzymes utilized in ubiquitin-dependent proteolysis have been isolated and examined in detail (Hershko 1988), and recent studies show that several of these are induced by heat shock and other stressors. In this chapter I review these developments and the relationship of the ubiquitin degradation system to the cell’s stress response program.