Roth Judith, Dobbelstein Matthias
Gastroenterologie und Stoffwechsel, Zentrum Innere Medizin, Klinikum der Universität Marburg, Baldingerstraße, 35043 Marburg, Germany1.
Institut für Virologie, Universität Marburg, Robert Koch Str. 17, 35037 Marburg, Germany2.
J Gen Virol. 1999 Dec;80 ( Pt 12):3251-3255. doi: 10.1099/0022-1317-80-12-3251.
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.
p51/p63/KET蛋白是基于它们与肿瘤抑制因子p53以及一组相关蛋白p73的高度同源性而被鉴定出来的。所有这些蛋白种类都被证明能激活至少一些p53反应性启动子的转录。为了评估转录活性剪接变体p51A/p63γ在肿瘤抑制中的可能作用，我们确定了使p53失活的病毒癌蛋白是否也可能靶向p51A。未发现猴空泡病毒40（SV40）的大T抗原和人乳头瘤病毒18型的E6蛋白抑制p51A介导的转录，而它们能强烈抑制p53的活性。此外，SV40 T抗原直接与p53相互作用，但与p51A没有可检测到的相互作用。最后，SV40 T抗原的一个细胞质突变体（K128A）使p53从细胞核重新定位到细胞质，但与细胞质T抗原共表达时，p51A仍留在细胞核中。这些结果有力地表明，这些病毒癌蛋白的抑制作用对p53具有特异性，对p51A没有明显影响。因此，与p53不同，p51A似乎不是病毒诱导细胞转化的必要靶点，在肿瘤抑制中可能不发挥与p53相当的作用。
