Heat shock proteins: the search for functions.

TLDR: The major HSPs have been strongly conserved in structure through evolution, clearly indicating that they play a vital role in survival of the organism.

Abstract: Not so long ago, in the olden (golden ?) days, scientists interested in the biochemistry and cell biology of proteins attempted to explain an enzyme's catalytic and regulatory functions and the cytoskeleton's properties in terms of protein structure. But SDS PAGE, monoclonal antibodies, and cDNA libraries (nucleic acid sequences reverse transcribed from mRNAs and inserted into the genomes of bacteriophage or plasmids) changed things, and many of us now study proteins the other way around. We know structure, in the form of subunit molecular weights, isoelectric points, modifications by phosphate, sugars, methylations, etc., and in some cases, even primary sequences and the precise localization in the cell or tissue. What we search for is function. Such a search has been in progress over the past several years to discover what heat shock proteins (HSPs) l do. Here, I define an HSP by two criteria: (a) its synthesis is strongly stimulated by an environmental stress, in particular, that resulting from a change in temperature a few degrees centigrade above the normal physiological one, and (b) its gene contains a conserved sequence of 14 base pairs in the 5' noncoding region, the Pelham box (62). This sequence serves as the promoter for HSP mRNA transcription. The response of cells to a heat shock was first described about 25 years ago during a study of temperature effects on Drosophila embryos (65). A dramatic change was seen in the puffing pattern of polytene chromosomes in salivary glands, and this was later shown to be the result of very active gene transcription that led to the synthesis of a small set of proteins. For about 15 years, this selective induction of proteins by a heat shock was thought to be unique to the fly. In 1978, however, an analogous response in avian and mammalian tissue culture cells to heat shock was discovered in my laboratory (33), and others reported a similar activity in E. coli (39, 78) and Tetrahymena (21). Reports of proteins induced after heat shocking a variety of species quickly followed and we now recognize that virtually all organisms-from E, coli to man-have HSPs (see reference 68 for a more complete history). The major HSPs have been strongly conserved in structure through evolution, clearly indicating that they play a vital role in survival of the organism. Their presence appears to enhance the cell's ability to recover from stress but