Cellular stress response: stress proteins--physiology and implications for cancer.

Abstract

The heat shock phenomenon was first observed in Drosophila when Ritossa (1962) studied chromosome puffing patterns. In 1974, Tissieres et al. discovered the heat shock proteins (HSPs) by electrophoretically analyzing newly synthesized proteins in heat-shocked Drosophila larvae. Heat shock treatment usually results in a strong induction of a set of proteins which have been synthesized before at a low level. Concomitantly, the synthesis of most other proteins is reduced significantly. Induction of HSPs has been found in practically all studied organisms, suggesting the universal importance of this phenomenon. HSP synthesis is part of a general adaptive response towards stresses which also includes changes in cell morphology and in the structure of chromatin and the cytoskeleton. Also, other noxious stress conditions such as arsenite, ethanol, heavy metals, amino acid analogs, oxidative stress, and certain anticancer drugs, as well as physiological stress conditions such as infection, inflammation, and ischemia, may result in the synthesis of HSPs. In addition, several of the HSPs are normally expressed and regulated during physiological processes like differentiation and cell cycle. Today it is generally accepted that HSPs have a protective function for cells and that they are a major cause for a phenomenon called “acquired thermotolerance”. The basic observation is that cells or organisms, if exposed to a mild preheating treatment, survive subsequent treatment with an otherwise lethal temperature.