Gill R M, Hamel P A, Zhe J, Zacksenhaus E, Gallie B L, Phillips R A
Division of Immunology and Cancer Research, Hospital for Sick Children, Toronto, Ontario, Canada.
Cell Growth Differ. 1994 May;5(5):467-74.
The retinoblastoma gene (RB1) is a recessive oncogene implicated in a number of human tumors. Although the RB1 gene is expressed in most proliferating cells, there is considerable evidence for the transcriptional regulation of this gene. Therefore, we have performed a detailed analysis of the regulatory elements in the promoter of the human RB1 gene. Deletion analysis of the 5' upstream region determined the location of the basal promoter to be between -208 and -179 nucleotides relative to the translational start. This region contains essential binding sites for the transcription elements ATF and SP1 and potentially important sites for E2F and steroid hormone responsiveness but no TATA or CAAT boxes. Primer extension and RNase protection analysis identified two initiation sites at -176 and -128 base pairs, both downstream of the promoter. Cotransfection experiments revealed repression of the RB1 promoter by its protein product p110RB1. This repression has been mapped to the core promoter region containing the E2F-binding site; however, this site is not required for autorepression.
视网膜母细胞瘤基因（RB1）是一种隐性癌基因，与多种人类肿瘤有关。尽管RB1基因在大多数增殖细胞中都有表达，但有大量证据表明该基因存在转录调控。因此，我们对人类RB1基因启动子中的调控元件进行了详细分析。对5'上游区域的缺失分析确定，相对于翻译起始位点，基础启动子的位置在-208至-179个核苷酸之间。该区域包含转录元件ATF和SP1的必需结合位点以及E2F和类固醇激素反应性的潜在重要位点，但没有TATA或CAAT框。引物延伸和RNase保护分析确定了两个起始位点，分别位于-176和-128碱基对处，均在启动子下游。共转染实验显示，RB1启动子被其蛋白产物p110RB1抑制。这种抑制作用已定位到包含E2F结合位点的核心启动子区域；然而，自抑制并不需要该位点。
