Failure of viral oncoproteins to target the p53-homologue p51A.
The p51/p63/KET proteins were identified based on their strong homology to the tumour suppressor p53 and a related set of proteins termed p73. All these protein species were shown to activate transcription from at least some p53-responsive promoters. To evaluate a possible role of the transcriptionally active splicing variant p51A/p63gamma in tumour suppression, we determined whether viral oncoproteins that inactivate p53 might also target p51A. Neither the large T-antigen of simian vacuolating virus 40 (SV40) nor the E6 protein from human papillomavirus type 18 were found to inhibit p51A-mediated transcription, whereas they strongly suppress the activity of p53. Further, SV40 T-antigen directly interacts with p53 but not detectably with p51A. Finally, a cytoplasmic mutant (K128A) of SV40 T-antigen relocalizes p53 from the nucleus to the cytoplasm, but p51A remains in the nucleus when coexpressed with cytoplasmic T-antigen. These results strongly suggest that the inhibitory effect of these viral oncoproteins is specific for p53 and does not measurably affect p51A. Thus, unlike p53, p51A does not appear to be a necessary target in virus-induced cell transformation and may not exert a role comparable to p53 in tumour suppression.
Roth
Judith
J
Gastroenterologie und Stoffwechsel, Zentrum Innere Medizin, Klinikum der Universität Marburg, Baldingerstraße, 35043 Marburg, Germany1.
Dobbelstein
Matthias
M
Institut für Virologie, Universität Marburg, Robert Koch Str. 17, 35037 Marburg, Germany2.
D000952:Antigens, Polyomavirus Transforming / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor / Q000235:genetics; D016158:Genes, p53 / Q000276:immunology; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D010750:Phosphoproteins; D012326:RNA Splicing; D015534:Trans-Activators; D014157:Transcription Factors; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins
D000952:Antigens, Polyomavirus Transforming; D004268:DNA-Binding Proteins; C052603:E6 protein, Human papillomavirus type 18; D009856:Oncogene Proteins, Viral; D010750:Phosphoproteins; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins