Mutants with changes within or near a hydrophobic region of simian virus 40 large tumor antigen are defective for binding cellular protein p53.
SV40 mutants bearing either amino acid substitution or in-frame deletion/insertion mutations in a region of the gene for large T antigen encoding a stretch of hydrophobic residues were analyzed for their behavior in permissive and nonpermissive cells. One of the mutants, with an Ile(573)-Phe substitution had a phenotype indistinguishable from that of wild-type SV40. The remaining three mutants were not viable and were defective for DNA replication. In addition, they displayed a cell-type specificity with respect to transformation; namely, they transformed the mouse C3H10T1/2 cell line, although with a reduced efficiency relative to wild-type, but were unable to transform the rat REF52 cell line. None of the T antigens from the defective mutants formed a complex with the cellular protein p53, indicating that the T-antigen-p53 complex is not required for the transformation of C3H10T1/2 cells.
Peden
K W
KW
Howard Hughes Medical Institute Laboratory, Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Srinivasan
A
A
Farber
J M
JM
Pipas
J M
JM
D000595:Amino Acid Sequence; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics*; D002460:Cell Line; D002472:Cell Transformation, Viral; D004261:DNA Replication; D004279:DNA, Viral / Q000235:genetics; D005816:Genetic Complementation Test; D008969:Molecular Sequence Data; D009154:Mutation; D009363:Neoplasm Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D010957:Plasmids; D011233:Precipitin Tests; D013539:Simian virus 40 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D014162:Transfection; D016159:Tumor Suppressor Protein p53; D010948:Viral Plaque Assay; D014779:Virus Replication
D000952:Antigens, Polyomavirus Transforming; D004279:DNA, Viral; D009363:Neoplasm Proteins; D010750:Phosphoproteins; D016159:Tumor Suppressor Protein p53