Bellett A J, Li P, David E T, Mackey E J, Braithwaite A W, Cutt J R
Mol Cell Biol. 1985 Aug;5(8):1933-9. doi: 10.1128/mcb.5.8.1933-1939.1985.
Altered control of the rat cell cycle induced by adenovirus requires expression of transformation region E1A, but not of E1B, E2A, E2B, or late genes. We show here that neither E3 nor E4 is required, so the effect results directly from an E1A product. Mutants with defects in the 289-amino-acid (aa) E1A product had little or no effect on the rat cell cycle even at 1,000 IU per cell. A mutant (pm975) lacking the 243-aa E1A product altered cell cycle progression, but less efficiently than did wild-type virus. The 289-aa E1A protein is therefore essential for cell cycle effects; the 243-aa protein is also necessary for the full effect but cannot act alone. Mutants with altered 289-aa E1A proteins showed different extents of leak expression of viral early region E2A as the multiplicity was increased; each leaked more in human than in rat cells. dl312, with no E1A products, failed to produce E2A mRNA or protein at 1,000 IU per cell in rat cells but did so in some experiments in human cells. There appears to be a very strict dependence of viral early gene expression on E1A in rat cells, whereas dependence on E1A is more relaxed in HeLa cells, perhaps due to a cellular E1A-like function. Altered cell cycle control is more dependent on E1A function than is early viral gene expression.
腺病毒诱导的大鼠细胞周期调控改变需要转化区E1A的表达，但不需要E1B、E2A、E2B或晚期基因的表达。我们在此表明E3和E4均不需要，因此这种效应直接由E1A产物引起。在289个氨基酸（aa）的E1A产物中存在缺陷的突变体即使在每细胞1000个感染单位（IU）的情况下对大鼠细胞周期也几乎没有影响或没有影响。一个缺乏243个aa的E1A产物的突变体（pm975）改变了细胞周期进程，但效率低于野生型病毒。因此，289个aa的E1A蛋白对于细胞周期效应至关重要；243个aa的蛋白对于完全效应也是必需的，但不能单独发挥作用。随着感染复数增加，289个aa的E1A蛋白发生改变的突变体显示出病毒早期区域E2A不同程度的渗漏表达；每种突变体在人细胞中的渗漏都比在大鼠细胞中更多。没有E1A产物的dl312在大鼠细胞中每细胞1000个IU时未能产生E2A mRNA或蛋白，但在一些人细胞实验中能产生。在大鼠细胞中，病毒早期基因表达似乎非常严格地依赖于E1A，而在HeLa细胞中对E1A的依赖则较为宽松，这可能是由于一种细胞内类似E1A的功能。与早期病毒基因表达相比，改变的细胞周期调控更依赖于E1A功能。
