Inactivation of the cellular p53 gene is a common feature of Friend virus-induced erythroleukemia: relationship of inactivation to dominant transforming alleles.
The Friend erythroleukemia virus complex contains no cell-derived oncogene. Transformation by this virus may therefore involve mutations affecting cellular gene expression. We provide evidence that inactivating mutations of the cellular p53 gene are a common feature in Friend virus-induced malignancy, consistent with an antioncogene role for p53 in this disease. We have shown that frequent rearrangements of the p53 gene cause loss of expression or synthesis of truncated proteins, whereas overexpression of p53 protein is seen in other Friend cell lines. We now demonstrate that p53 expression in the latter cells is also abnormal, as a result of missense mutations in regions encoding highly conserved amino acids. Three of these aberrant alleles obtained from cells from different mice were cloned and found to function as dominant oncogenes in gene transfer assays, supporting the view that certain naturally occurring missense mutations in p53 confer a dominant negative phenotype on the encoded protein.
Munroe
D G
DG
Ontario Cancer Institute, University of Toronto, Canada.
Peacock
J W
JW
Benchimol
S
S
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004622:Embryo, Mammalian; D000939:Epitopes / Q000032:analysis; D005622:Friend murine leukemia virus / Q000235:genetics*; D005784:Gene Amplification; D005799:Genes, Dominant; D004915:Leukemia, Erythroblastic, Acute / Q000382:microbiology; D007942:Leukemia, Experimental / Q000382:microbiology; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics*; D015345:Oligonucleotide Probes; D015513:Oncogene Proteins / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D010750:Phosphoproteins / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D012313:RNA / Q000235:genetics; D016372:RNA, Antisense; D012333:RNA, Messenger / Q000037:antagonists & inhibitors; D051381:Rats; D011916:Rats, Inbred F344; D012260:Ribonucleases; D016159:Tumor Suppressor Protein p53
D000939:Epitopes; D009687:Nuclear Proteins; D015345:Oligonucleotide Probes; D015513:Oncogene Proteins; D010750:Phosphoproteins; D016372:RNA, Antisense; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D012313:RNA; D012260:Ribonucleases