Batsché E, Lipp M, Cremisi C
Unité de Technologie Cellulaire, Institut Pasteur, Paris, France.
Oncogene. 1994 Aug;9(8):2235-43.
The c-myc promoter was investigated as a possible cellular target for SV40 large T (LT) antigen. In fibroblast and epithelial cell lines, the human c-myc promoter was transactivated by LT. This transactivation was dependent of the interaction of LT with the retinoblastoma (RB) protein. The use of deletions and point mutations of the c-myc promoter demonstrated that in both cell types, the E2F binding sites are necessary for such transactivation. Unexpectedly however, over-expression of RB caused an overall transcriptional activation of the c-myc promoter. We resolved this apparent paradox by demonstrating that this activation is a combination of two antagonistic effects: transcriptional repression mediated by the E2F factor, and transcriptional activation independent of this factor. RB was also found to prevent LT-mediated transactivation, and LT inhibited RB-mediated activation independently of the E2F factor. LT therefore antagonizes both the transcriptional repression and activation mediated by RB.
研究了c-myc启动子作为猴空泡病毒40大T（LT）抗原潜在细胞靶点的可能性。在成纤维细胞和上皮细胞系中，人c-myc启动子被LT反式激活。这种反式激活依赖于LT与视网膜母细胞瘤（RB）蛋白的相互作用。对c-myc启动子进行缺失和点突变分析表明，在这两种细胞类型中，E2F结合位点对于这种反式激活是必需的。然而，出乎意料的是，RB的过表达导致c-myc启动子整体转录激活。我们通过证明这种激活是两种拮抗作用的组合来解决这一明显的矛盾：由E2F因子介导的转录抑制和不依赖于该因子的转录激活。还发现RB可阻止LT介导的反式激活，且LT可独立于E2F因子抑制RB介导的激活。因此，LT拮抗了由RB介导的转录抑制和激活。
