Shan B, Chang C Y, Jones D, Lee W H
Center for Molecular Medicine/Institute of Biotechnology, University of Texas Health Science Center at San Antonio 78245.
Mol Cell Biol. 1994 Jan;14(1):299-309. doi: 10.1128/mcb.14.1.299-309.1994.
The retinoblastoma (RB) gene is the prototype tumor suppressor gene. Mutations in this gene are often associated with the occurrence of various tumors. Several mutations have been found in the promoter region of the gene, suggesting that inappropriate transcriptional regulation of the RB gene contributes to tumorigenesis. Sequence analysis of the RB promoter has revealed a potential E2F recognition site within a region critical for RB gene transcription. By using the cloned E2F-1 gene, here we report that (i) RB expression is negatively regulated by its own gene product, (ii) E2F-1 binds specifically to an E2F recognition sequence in the RB promoter and transactivates the RB promoter, (iii) overexpression of RB suppresses E2F-1-mediated stimulation of RB promoter activity, and (iv) the expression of the RB gene is paralleled by the expression of the E2F-1 gene during cell cycle progression. These results demonstrate that expression of RB is negatively autoregulated through E2F-1.
视网膜母细胞瘤（RB）基因是肿瘤抑制基因的原型。该基因的突变常与各种肿瘤的发生相关。在该基因的启动子区域已发现多种突变，这表明RB基因转录调控异常有助于肿瘤发生。对RB启动子的序列分析揭示了在对RB基因转录至关重要的区域内存在一个潜在的E2F识别位点。通过使用克隆的E2F - 1基因，我们在此报告：（i）RB的表达受其自身基因产物的负调控；（ii）E2F - 1特异性结合RB启动子中的E2F识别序列并反式激活RB启动子；（iii）RB的过表达抑制E2F - 1介导的RB启动子活性刺激；（iv）在细胞周期进程中，RB基因的表达与E2F - 1基因的表达平行。这些结果表明，RB的表达通过E2F - 1进行负向自动调节。
