The role of p53 in growth of mouse fibroblast lines

To examine the hypothesis that p53 protein may play a central role in regulating reproduction of mammalian cells, we compared the absolute amounts and relative rates of synthesis of p53 protein in two pseudonormal cell lines, 3T3 and C3H 10T1/2, during quiescence, during log proliferation, and in quiescent cells stimulated with serum. The absolute amount of p53 protein per cell was found to be severalfold lower in quiescent cells than in log-phase cells. The ratio of the rate of synthesis of p53 protein to the rate of synthesis of total protein was slightly higher in quiescent cells than the same ratio in log-phase cells. Thus, entry into quiescence is not accompanied by a differential switch-off of synthesis of p53 protein. In quiescent cells stimulated with serum the amount of p53 protein per cell and its rate of synthesis increase, but only in proportion to the increase in total protein per cell and the increase in rate of total protein synthesis. Similarly, 12-14 h after serum stimulation, the time of the G1 to S transition, the accumulated increase in p53 protein per cell is about what would be expected for a short-lived protein whose rate of synthesis has increased in proportion to the increase in rate of synthesis of total protein. The results are not those expected for a protein that functions specifically in release from quiescence or in transition from G1 to S.