Deletion of 5'-coding sequences of the cellular p53 gene in mouse erythroleukemia: a novel mechanism of oncogene regulation.
The p53 gene is rearranged in an erythroleukemic cell line (DP15-2) transformed by Friend retrovirus. Here, we characterize the mutation and identify a deletion of approximately equal to 3.0 kilobases that removes exon 2 coding sequences. The gene is expressed in DP15-2 cells and results in synthesis of a 44,000-dalton protein that is missing the N-terminal amino acid residues of p53. The truncated protein is unusually stable and accumulates to high levels intracellularly. Moreover, it appears to have undergone a change in conformation as revealed by epitope mapping studies. This study represents the first description of an altered p53 gene product arising by mutation during neoplastic progression and identifies a region in the p53 protein molecule that plays a role in determining p53 stability in vivo.
D000818:Animals; D000911:Antibodies, Monoclonal; D001483:Base Sequence; D002872:Chromosome Deletion; D004273:DNA, Neoplasm / Q000235:genetics; D005622:Friend murine leukemia virus; D005786:Gene Expression Regulation; D004915:Leukemia, Erythroblastic, Acute / Q000235:genetics*; D051379:Mice; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000235:genetics* / Q000276:immunology; D010750:Phosphoproteins / Q000235:genetics* / Q000276:immunology; D011519:Proto-Oncogenes; D016159:Tumor Suppressor Protein p53
D000911:Antibodies, Monoclonal; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D010750:Phosphoproteins; D016159:Tumor Suppressor Protein p53