Weintraub S J, Chow K N, Luo R X, Zhang S H, He S, Dean D C
Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA.
Nature. 1995 Jun 29;375(6534):812-5. doi: 10.1038/375812a0.
The retinoblastoma tumour-suppressor protein (Rb) belongs to a family that share a motif known as the pocket. The pocket was originally identified as the region of Rb required for binding to oncoproteins from DNA tumour viruses, which disrupt the binding of Rb to the E2F family of cell-cycle transcription factors (referred to collectively here as E2F). Rb switches E2F sites from positive to negative elements, suggesting that Rb-E2F is an active complex that blocks transcription. Here we report that Rb is selectively recruited to promoters through E2F, where it in turn inactivates surrounding transcription factors by blocking their interaction with the basal transcription complex. We suggest that this repressor activity is essential for inhibiting promoters that contain enhancers in addition to E2F sites.
视网膜母细胞瘤肿瘤抑制蛋白(Rb)属于一个共享被称为“口袋”基序的家族。该口袋最初被鉴定为Rb与DNA肿瘤病毒癌蛋白结合所需的区域,这些癌蛋白会破坏Rb与细胞周期转录因子E2F家族(此处统称为E2F)的结合。Rb将E2F位点从正调控元件转变为负调控元件,这表明Rb - E2F是一个阻止转录的活性复合物。在此,我们报告Rb通过E2F被选择性招募到启动子区域,在那里它通过阻断周围转录因子与基础转录复合物的相互作用来使其失活。我们认为这种抑制活性对于抑制除E2F位点外还含有增强子的启动子至关重要。