Ota M, Eto K, Ninomiya Y, Ikeda M
Department of Developmental Biology, Graduate School of Dentistry, Tokyo Medical and Dental University, Japan.
Cell Growth Differ. 1998 Dec;9(12):989-97.
The SV40 enhancer is repressed in embryonal carcinoma (EC) cells, and it is also repressed by the adenovirus E1A oncoprotein. Repression by E1A is mediated by the binding of E1A to the p300 transcriptional coactivator. Thus, we examined the role of p300 in the repression of the SV40 enhancer activity in EC cells. We demonstrated that high levels of p300 protein are accumulated in undifferentiated EC cells and that the levels decline dramatically upon differentiation because of the changes of protein stability. Furthermore, we showed that overexpression of p300 does not stimulate the SV40 enhancer activity in undifferentiated F9 cells. However, the activity of a p300 mutant deficient for E1A binding can be restored by the presence of excess E1A. In addition, low-level expression of E1A causes derepression of the enhancer activity in F9 cells. These results indicate that the accumulation of p300 protein participates in repression of the SV40 enhancer activity in undifferentiated F9 cells.
猿猴病毒40（SV40）增强子在胚胎癌细胞（EC细胞）中受到抑制，并且它也被腺病毒E1A癌蛋白所抑制。E1A的抑制作用是通过E1A与p300转录共激活因子的结合来介导的。因此，我们研究了p300在EC细胞中抑制SV40增强子活性的作用。我们证明，高水平的p300蛋白在未分化的EC细胞中积累，并且由于蛋白质稳定性的变化，在分化时其水平会急剧下降。此外，我们表明，p300的过表达不会刺激未分化的F9细胞中的SV40增强子活性。然而，缺乏E1A结合能力的p300突变体的活性可以通过过量E1A的存在而恢复。另外，E1A的低水平表达会导致F9细胞中增强子活性的去抑制。这些结果表明，p300蛋白的积累参与了未分化F9细胞中SV40增强子活性的抑制。
