Relationship between thermal tolerance and protein degradation in temperature-sensitive mouse cells

The induction of thermotolerance was studied in a temperature sensitive mouse cell line, ts85, and results were compared with those for the wild-type FM3A cells. At the nonpermissive temperature of 39°C, ts85 cells are defective in the degradation of short-lived abnormal proteins, apparently because of loss of activity of a ubiquitin-activating enzyme. The failure of the ts85 cells to develop thermotolerance to 41–43°C after incubation at the nonpermissive temperature of 39°C correlated with the failure of the cells to degrade short-lived abnormal proteins at 39°C. However, the failure of the ts85 cells to develop thermotolerance to 43°C during incubation at 33°C after either arsenite treatment or heating at 45.5°C for 6 or 10 min did not correlate with protein degradation rates. Although the rate of degrading abnormal protein was reduced after heating at 45.5°C for 10 min, the rates were normal after arsenite treatment or heating at 45.5°C for 6 min. In addition, when protein synthesis was inhibited with cyclohexmide both during incubation at 33°C or 39°C and during heating at 41–43°C, resistance to heating was observed, but protein degradation rates at 39°C or 43°C were not altered by the cycloheximide treatment. Therefore, there is apparently no consistent relationship between rates of degrading abnormal proteins and the ability of cells to develop thermotolerance and resistance to heating in the presence of cycloheximide. © 1992 Wiley-Liss, Inc.