Metabolic turnover of human c-ras super(H) p21 protein of EJ bladder carcinoma and its normal cellular and viral homologs

The EJ bladder carcinoma oncogene is activated by a point mutation in the c-ras super(H) proto-oncogene at the 12th amino acid codon. In an attempt to understand the mechanism of oncogenic activation, a comparative study was undertaken to examine the metabolic turnover and subcellular localization of the p21 protein encoded by the EJ oncogene, the viral oncogene, and its normal cellular homolog. Pulse-labeling experiments indicated that both c-ras) p21 proteins were synthesized by a very similar pathway, as was observed for the viral p21 protein of Harvey murine sarcoma virus. Although both p21 proteins of EJ and the normal c-ras genes which are not phosphorylated have a half-life of 20 h, the viral p21 protein of Harvey murine sarcoma virus which includes a phosphorylated form is much more stable in cells, having a half-life of 42 h, apparently due to phosphorylation.