Berger L C, Smith D B, Davidson I, Hwang J J, Fanning E, Wildeman A G
Department of Molecular Biology and Genetics, University of Guelph, Ontario, Canada.
J Virol. 1996 Feb;70(2):1203-12. doi: 10.1128/JVI.70.2.1203-1212.1996.
The large tumor antigen (TAg) of simian virus 40 regulates transcription of the viral genes. The early promoter is repressed when TAg binds to the origin and DNA replication begins, whereas the late promoter is activated by TAg through both replication-dependent and -independent mechanisms. Previously it was shown that activation is diminished when a site in the viral enhancer to which the factor TEF-1 binds is disrupted. We show here that the NH2-terminal region of TAg binds to the TEA domain of TEF-1, a DNA binding domain also found in the Drosophila scalloped and the Saccharomyces cerevisiae TEC1 proteins. The interaction inhibits DNA binding by TEF-1 and activates transcription in vitro from a subset of naturally occurring late start sites. These sites are also activated by mutations in the DNA motifs to which TEF-1 binds. Therefore, TEF-1 appears to function as a repressor of late transcription, and its involvement in the early-to-late shift in viral transcription is discussed. The mutation of Ser-189 in TAg, which reduces transformation efficiency in certain assays, disrupts the interaction with TEF-1. Thus, TEF-1 might also regulate genes involved in growth control.
猿猴病毒40的大肿瘤抗原（TAg）调节病毒基因的转录。当TAg与病毒起源结合且DNA复制开始时，早期启动子被抑制，而晚期启动子则通过依赖复制和不依赖复制的机制被TAg激活。先前的研究表明，当病毒增强子中与转录增强因子1（TEF-1）结合的位点被破坏时，激活作用会减弱。我们在此表明，TAg的氨基末端区域与TEF-1的TEA结构域结合，TEA结构域是一种在果蝇扇形蛋白和酿酒酵母TEC1蛋白中也存在的DNA结合结构域。这种相互作用抑制了TEF-1与DNA的结合，并在体外从一部分天然存在的晚期起始位点激活转录。这些位点也可通过TEF-1结合的DNA基序中的突变而被激活。因此，TEF-1似乎起着晚期转录抑制因子的作用，并讨论了其在病毒转录从早期到晚期转变中的作用。TAg中丝氨酸189的突变在某些实验中会降低转化效率，该突变破坏了与TEF-1的相互作用。因此，TEF-1可能也调节参与生长控制的基因。
