Bennoun M, Grimber G, Couton D, Seye A, Molina T, Briand P, Joulin V
INSERM U-380, ICGM, Paris, France.
Oncogene. 1998 Sep 10;17(10):1253-9. doi: 10.1038/sj.onc.1202047.
The transforming activity of SV40 large T-antigen (Tag) depends on its binding to cellular proteins involved in the control of the cell cycle (p53, pRb, p300..) and on the J-domain region in the amino-terminus. We established transgenic lines expressing wild-type or Tag mutant proteins lacking one of the three transforming domains, to determine the respective contributions of these domains to hepatic tumour formation. Tag mutants with no pRb-binding domain or N-terminal fragment did not cause neoplastic liver abnormalities. The d11137 Tag mutant protein, which inhibits pRb function without affecting p53, induced hepatic tumours. These tumours grew significantly faster than those induced by wild-type Tag. Our results demonstrate different requirements for each of the inactivating functions of SV40 Tag in hepatocyte transformation and show that the loss of p53 function has only a moderate effect on hepatic tumour formation.
SV40大T抗原（Tag）的转化活性取决于其与参与细胞周期调控的细胞蛋白（p53、pRb、p300等）的结合以及氨基末端的J结构域区域。我们建立了表达野生型或缺乏三个转化结构域之一的Tag突变蛋白的转基因品系，以确定这些结构域对肝肿瘤形成的各自贡献。没有pRb结合结构域或N末端片段的Tag突变体不会引起肿瘤性肝脏异常。抑制pRb功能而不影响p53的d11137 Tag突变蛋白诱导肝肿瘤。这些肿瘤的生长速度明显快于野生型Tag诱导的肿瘤。我们的结果表明，SV40 Tag的每种失活功能在肝细胞转化中具有不同的要求，并表明p53功能的丧失对肝肿瘤形成仅具有中等程度的影响。
