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Mol Cell Biol. 1984 March; 4(3): 442-448

Energy requirement for degradation of tumor-associated protein p53.

ABSTRACT

A 53,000-dalton protein (p53) present in large amounts in several types of tumorigenic cells was rapidly degraded in nontumorigenic BALB/c 3T3 fibroblasts (t 1/2, approximately 0.5 h) but not in tumorigenic methylcholanthrene-induced mouse sarcoma cells (t 1/2, greater than 2 h). In 3T3 cells, dinitrophenol and 2-deoxyglucose, agents which reduce ATP production, inhibited the rapid degradation of p53 and the slower breakdown of total cell protein. After removal of these agents, the degradation of both p53 and total cell proteins resumed at their normal rates. Inhibitors of intralysosomal proteolysis (Ep475 and chloroquine) did not reduce the rate of degradation of p53. Thus, in 3T3 cells, p53 appears to be degraded by a nonlysosomal, ATP-dependent proteolytic system similar to that previously shown to degrade short- and long-lived proteins in growing fibroblasts. The immunoreactive p53 which remained in ATP-depleted cells had the same molecular weight as the p53 in the control cells. No intermediate products of p53 degradation were detected by immunoprecipitation in either ATP-depleted or control cells. Hence, ATP seems to be required for an initial step in the degradation of p53. Although the amount of labeled p53 was increased in simian virus 40-transformed and methylcholanthrene-induced mouse sarcoma cells, the amount of p53 labeled during a 3-h pulse in Moloney virus- and Rous sarcoma virus-transformed cells and untransformed 3T3 cells was similar. Thus, an increased net rate of p53 accumulation is not a common feature of transformed tumorigenic cells.

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