E2F AS AN SV40/ADENOVIRUS TRANSFORMATION TARGET

SV40与人类腺病毒及看似无关的DNA肿瘤 病毒。每一种都可以转化各种培养的细胞系和 菌株，并且每种菌株在啮齿动物身上都是致瘤的。SV40大T抗原(T) 和腺病毒E1a蛋白进行了很大一部分 改造相关病毒的工作。这两种蛋白质都能在 转化，部分是通过与视网膜母细胞瘤形成复合体 基因产物(Rb)和相关蛋白质，例如p107。充足的证据 指出了E1a和T取代转录因子的能力， E2F，从其在Rb和p107表面的结合域。进一步 有证据表明，E2F的T/E1a置换本身是一种蛋白质， 激活某些基因，其产物促进退出G0/G1，可能 释放这种蛋白质的不受调控的作用，这是怀疑的 对T和E1a的促生长作用有一定作用。这 应用程序侧重于了解更多E2F在细胞中的功能 周期，它与RB的相互作用如何转化为生长控制 事件，是否具有癌基因潜力，是否存在多个E2F 物种，如果是的话，原因是什么。

SV40 and the human adenoviruses and seemingly unrelated DNA tumor viruses. Each can transform a variety of cultured cell lines and strains, and each is tumorigenic in rodents. SV40 large T antigen (T) and adenovirus E1A protein carry out a significant part of the transforming work of the relevant virus. Both proteins work in transformation, in part, by forming a complex with the retinoblastoma gene product (RB) and related proteins, e.g. p107. Abundant evidence points to the ability of E1A and T to displace the transcription factor, E2F, from its binding domains on the surfaces of RB and p107. Further evidence suggests that T/E1A displacement of E2F, itself a protein which activates certain genes whose products promote exit from G0/G1, may unleash unregulated action of this protein which is suspected of contributing to the growth stimulatory effects of T and E1A. This application focuses on learning more of how E2F functions in the cell cycle, how its interaction with RB is translated into growth controlling events, Whether it has oncogene potential, whether there are multiple E2F species and, if so, why.