Robbins P D, Horowitz J M, Mulligan R C
Whitehead Institute for Biomedical Research, Nine, Cambridge, Massachusetts 02142.
Nature. 1990 Aug 16;346(6285):668-71. doi: 10.1038/346668a0.
Inactivation of the retinoblastoma susceptibility gene (RB-1) has been associated with the aetiology of many types of human cancers, leading to the classification of RB-1 as an anti-oncogene or tumour suppressor gene. Given that the protein product of RB-1 (Rb) has a nuclear localization and DNA-binding activity in vitro, it is possible that Rb regulates transcription of certain genes. The promoter of the c-fos gene might be a target for regulation by Rb, because both v-fos and RB-1 are associated with the induction of osteosarcomas in mice and humans, respectively. Also, fos expression is thought to be required for quiescent cells to enter the cell cycle, making the fos promoter an attractive target for suppressors of cell growth. Here we report that Rb can repress c-fos expression and AP-1 transcriptional activity in both serum-induced and cycling 3T3 cells. We have mapped a cis-acting element in the human c-fos promoter that can confer repression by Rb to a heterologous promoter. We have the termed the cis-acting sequence regulated by Rb the retinoblastoma control element.
视网膜母细胞瘤易感基因（RB-1）的失活与多种人类癌症的病因相关，这使得RB-1被归类为一种抗癌基因或肿瘤抑制基因。鉴于RB-1的蛋白质产物（Rb）在体外具有核定位和DNA结合活性，Rb有可能调节某些基因的转录。c-fos基因的启动子可能是Rb调控的靶标，因为v-fos和RB-1分别与小鼠和人类骨肉瘤的诱导有关。此外，静止细胞进入细胞周期被认为需要fos表达，这使得fos启动子成为细胞生长抑制因子的一个有吸引力的靶标。在此我们报告，Rb在血清诱导的和处于细胞周期的3T3细胞中均可抑制c-fos表达和AP-1转录活性。我们已经在人c-fos启动子中定位了一个顺式作用元件，该元件可赋予Rb对异源启动子的抑制作用。我们将受Rb调控的顺式作用序列称为视网膜母细胞瘤控制元件。
