Mechanism of inhibition of polypeptide chain initiation in heat‐shocked Ehrlich ascites tumour cells

Abstract

The rate of polypeptide synthesis is inhibited by 80% in [mouse] Ehrlich cells incubated at 43.degree. C compared to those at 37.degree. C. The regulatory site of translation resides at polypeptide chain initiation. Polypeptide synthesis does not recover at the higher temperature; however, the inhibition is reversed by returning the cells to 37.degree. C. Neither new RNA synthesis nor protein synthesis is required for recovery at 37.degree. C, eliminating degradation of mRNA and irreversible denaturation of a protein essential for polypeptide chain initiation. The concentration of 40-S initiation complexes was reduced markedly in heat-shocked cells compared to controls. This was confirmed in the cell-free protein-synthesizing systems prepared from heat-shocked and control cells. Reversible alteration in the activity of components affecting eIF2 [eukaryotic initiation factor-2] function is, therefore, a likely mechanism of regulation in heat-shocked Ehrlich cells. In extracts from heat-shocked cells, Met-tRNA synthetase activity was unaltered compared to control extracts.