Simian virus 40 large T antigen induces or activates a protein kinase which phosphorylates the transformation-associated protein p53.
The cellular phosphoprotein p53 is presumably involved in simian virus 40 (SV40)-induced transformation. We have monitored changes in the state of phosphorylation of p53 from normal versus SV40-infected or -transformed cells. In normal cells, p 53 was hardly phosphorylated. Upon infection or transformation, a quantitative and qualitative increase in p53 phosphorylation was observed as revealed by two-dimensional phosphopeptide analysis. This increase was dependent on a functional large T antigen. In rat cells, enhanced phosphorylation of p53 resulted in conversion to a second, electrophoretically distinct form. In cells transformed with transformation-defective mutants, phosphorylation of p53 was reduced and conversion to form 2 was inefficient. These data suggest (i) that SV40 large T antigen induces or activates a protein kinase, one substrate of which is p53, (ii) that transformation-defective mutants are impaired in kinase induction, and (iii) that either a certain phosphorylation state of p53 or the SV40-induced kinase is critical for efficient transformation.
Scheidtmann
K H
KH
Institut für Immunbiologie, Universität Freiburg, Federal Republic of Germany.
Haber
A
A
D000818:Animals; D000952:Antigens, Polyomavirus Transforming; D002460:Cell Line; D002472:Cell Transformation, Viral; D015180:Electrophoresis, Gel, Two-Dimensional; D004591:Electrophoresis, Polyacrylamide Gel; D007700:Kinetics; D009687:Nuclear Proteins / Q000378:metabolism*; D015513:Oncogene Proteins / Q000302:isolation & purification / Q000378:metabolism*; D010446:Peptide Fragments / Q000302:isolation & purification; D010748:Phosphopeptides / Q000302:isolation & purification; D010750:Phosphoproteins / Q000302:isolation & purification / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases; D010766:Phosphorylation; D011494:Protein Kinases / Q000096:biosynthesis / Q000378:metabolism*; D013539:Simian virus 40 / Q000235:genetics* / Q000276:immunology; D016159:Tumor Suppressor Protein p53
D000952:Antigens, Polyomavirus Transforming; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D010446:Peptide Fragments; D010748:Phosphopeptides; D010750:Phosphoproteins; D016159:Tumor Suppressor Protein p53; D011494:Protein Kinases; D010744:Phosphoric Monoester Hydrolases