The mammalian heat shock (or stress) response: a cellular defense mechanism.
The response of mammalian cells to abrupt changes in their local environment entails a series of coordinated transcription and translation events leading to the accumulation of a group of proteins, the stress proteins. As evidenced by the high similarities in the structure of the stress proteins amongst different organisms, the stress response appears to be a well-conserved, pre-planned strategy by which cells protect themselves against changes in their environmental circumstance. In addition to their presumed protective role, most of the stress proteins are expressed at significant levels in cells grown under normal conditions and participate in a number of biological phenomenon apparently distinct from their role during stress. For example, we have described here the role of some of the stress proteins in clathrin coated vesicle assembly/disassembly, tyrosine kinase and steroid hormone receptor function, and cell proliferation. In this regard it seems likely that we have only touched the surface regarding the many different biological processes which occur normally in cells and which involve the participation of the individual stress proteins. Of particular importance, as well, is to understand the role of the stress proteins, both individually and collectively, in protecting the cell during and after recovery from physiological stress. A breakthrough in this endeavor has come from the recent observation demonstrating the structural and biochemical similarities of many of the stress proteins and notably their ability to bind ATP. In this regard, I have described the immunological and biochemical similarities of the 70 kDa heat shock proteins with that of the 80 kDa glucose regulated protein and suggest that this family of proteins serves basically similar functions but within different intracellular compartments: the 70 kDa proteins being cytosolic and nuclear and 80 kDa being present within the endoplasmic reticulum. That a general rule is emerging here comes from the recent observation of Sorger and Pelham (in press) describing a significant sequence homology of the 90 kDa heat shock protein with that of the other glucose-regulated protein, 100 kDa. Here again, however, the proteins are distributed differently: 90 kDa is a soluble cytoplasmic protein and 100 kDa is present within the Golgi and perhaps the plasma membrane (Welch et al., 1984). Might all of the stress proteins have evolved from only a few genes with selection having resulted in different compartmentalization of the stress proteins?(ABSTRACT TRUNCATED AT 250 WORDS)
Welch
W J
WJ
Cold Spring Harbor Laboratory, New York 11724.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000032:analysis; D006360:Heat-Shock Proteins / Q000032:analysis / Q000502:physiology*; D006801:Humans; D008970:Molecular Weight; D013312:Stress, Physiological / Q000473:pathology
D002352:Carrier Proteins; D006360:Heat-Shock Proteins; D000255:Adenosine Triphosphate