Metabolic turnover of human c-rasH 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-rasH 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. The pro-p21 proteins were detected in free cytosol, and the processed products were associated with plasma membrane. The intracellular half-life of p21 proteins was determined by pulse-labeling and chasing in the presence of excess unlabeled methionine. 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.
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D005814:Genes, Viral; D006251:Harvey murine sarcoma virus / Q000235:genetics*; D006801:Humans; D007700:Kinetics; D051379:Mice; D008815:Mice, Inbred Strains; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009368:Neoplasm Transplantation; D009857:Oncogenes; D000090063:Proto-Oncogene Mas; D016283:Proto-Oncogene Proteins p21(ras); D009053:Sarcoma Viruses, Murine / Q000235:genetics*; D014183:Transplantation, Heterologous; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism
C000715470:MAS1 protein, human; D009363:Neoplasm Proteins; D000090063:Proto-Oncogene Mas; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)