Heat shock proteins.

The enhanced synthesis of a few proteins immediately after subjecting cells to a stress such as heat shock was first reported for drosophila cells in 1974 (l), and the universality of the response from bacteria to human was recognized shortly thereafter (reviewed in Ref. 2). In the ensuing 16 years, a vast literature has accumulated that describes a wide variety of events in a cell’s response to a heat shock. The scope of the data ranges from x-ray crystallographic measurements and physical chemical studies on specific heat shock proteins to the effects of heat shock gene expression on an organism’s ecological niche. Recently, the emphasis in this field has focused on the unction of various heat shock proteins and their possible role as “molecular chaperones”’ (3). In the subject matter that follows, I review recent data and other aspects of the heat shock phenomenon. A more thorough and comprehensive discussion of this topic can be found in a number of recent reviews and monographs (4-10). Primary references to much of the material described here are in these reviews. Much of the initial molecular biology and biochemistry of heat shock consisted of cloning the genes, determining primary sequences of the proteins, and probing the regulatory factors responsible for their induction. From these latter studies, we learned that the DNA sequence responsible for regulating heat shock gene expression in the eukaryotic cell was invariant from yeast to human (reviewed in Ref. 11). The most recent analysis of this element suggests it is an inverted repeat of the 5-nucleotide base pair, nGAAn (12). The presence of this element located about 80-150 base pairs upstream of the start site of RNA transcription is the most definitive evidence that the gene encodes a heat shock protein. However, most of these genes have other regulatory signals that activate the gene when the appropriate protein factors are present. For example, there are at least four sequence motifs upstream of the human hsp702 gene that are responsive individually to serum factors, heavy metals, and the ElA protein of adenovirus (13). The obvious interpretation of these results is that the hsp70 protein is synthesized for reasons other than heat shock and, in fact, this gene is activated at a specific stage (early S) in the cell’s mitotic cycle, during mitogenesis and upon other stress conditions (see Table I). Most of the heat shock proteins are induced by other stress agents (a listing is in Ref. 14) and during normal development of an organism (reviewed in Ref. 15). The gene encoding the protein that binds to the heat shockresponsive DNA sequence has been cloned from yeast (16,17) and shown to be essential for viability of this organism. This