Introduction: Heat Shock Proteins—From Drosophila Stress Proteins to Mediators of Human Disease

Abstract

Nowadays heat shock proteins (HSP) seem to be everywhere and can apparently do anything. But it was not always so. For many years HSP genes were academic arcana, curiosities apparently confined to the salivary glands of fruit flies. Their study was initiated by the discovery of a new gene expression pattern, through a happy accident involving the overheating of a Drosophila salivary gland preparation on a microscope stage (Ritossa, 1962). This was first reported as, “A new puffing pattern induced by temperature shock and DNP in Drosophila” in 1962 (Ritossa, 1962). However, it was to take another 10–15 years before the first Drosophila HSP mRNA was isolated (Ashburner, 1982). Around this time (1978) the HSP “went global” and were discovered in mammalian tissue culture cells, in E. coli, in yeast, and in plants (Kelley and Schlesinger, 1978; Lemeaux et al., 1978; Bouche et al., 1979; Miller et al., 1979; Barnett et al., 1980; Hightower and White, 1981). The heat shock field emerged as a major study area in experimental biology at the 1982 meeting Heat Shock: From Bacteria To Man, held at the Cold Spring Harbor Laboratory (Ashburner, 1982). At this time, however, the functions of the HSP remained mysterious and the details of regulation of hsp gene expression were only beginning to emerge. All that was known was that the proteins appeared to possess “homeostatic activity” and were (as they are to this day) associated with resistance to heat shock and other stresses (Chapter 2). However, with the intensive international effort and the wealth of experimental systems available in the early 1980s, the concept began to emerge that the HSP belonged to a new kind of proteins which function to modify the structures of other proteins.