Mechanism of inhibition of polypeptide chain initiation in heat-shocked Ehrlich ascites tumour cells.
The rate of polypeptide synthesis is inhibited by 80% in Ehrlich cells incubated at 43 degrees C compared to those at 37 degrees 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 degrees C. Neither new RNA synthesis or protein synthesis is required for recovery at 37 degrees C, eliminating degradation of mRNA and irreversible denaturation of a protein essential for polypeptide chain initiation. The concentration of 40-S initiation complexes was found to be 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 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.
D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000201:enzymology / Q000378:metabolism*; D002460:Cell Line; D002474:Cell-Free System; D006358:Hot Temperature; D008718:Methionine-tRNA Ligase / Q000378:metabolism; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D010442:Peptide Chain Initiation, Translational; D014633:Valine / Q000378:metabolism
D009363:Neoplasm Proteins; D008718:Methionine-tRNA Ligase; D014633:Valine