Shao Z, Ruppert S, Robbins P D
Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, PA 15261, USA.
Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3115-9. doi: 10.1073/pnas.92.8.3115.
RB, the protein product of the retinoblastoma tumor-suppressor gene, regulates the activity of specific transcription factors. This regulation appears to be mediated either directly through interactions with specific transcription factors or through an alternative mechanism. Here we report that stimulation of Sp1-mediated transcription by RB is partially abrogated at the nonpermissive temperature in ts13 cells. These cells contain a temperature-sensitive mutation in the TATA-binding protein-associated factor TAFII250, first identified as the cell cycle regulatory protein CCG1. The stimulation of Sp1-mediated transcription by RB in ts13 cells at the nonpermissive temperature could be restored by the introduction of wild-type human TAFII250. Furthermore, we demonstrate that RB binds directly to hTAFII250 in vitro and in vivo. These results suggest that RB can confer transcriptional regulation and possibly cell cycle control and tumor suppression through an interaction with TFIID, in particular with TAFII250.
视网膜母细胞瘤肿瘤抑制基因的蛋白质产物RB可调节特定转录因子的活性。这种调节似乎是通过与特定转录因子直接相互作用或通过另一种机制介导的。在此,我们报告在ts13细胞中,在非允许温度下,RB对Sp1介导的转录的刺激作用部分被消除。这些细胞在TATA结合蛋白相关因子TAFII250中存在温度敏感突变,TAFII250最初被鉴定为细胞周期调节蛋白CCG1。在非允许温度下,通过引入野生型人TAFII250可恢复ts13细胞中RB对Sp1介导的转录的刺激作用。此外,我们证明RB在体外和体内都直接与hTAFII250结合。这些结果表明,RB可通过与TFIID,特别是与TAFII250相互作用来赋予转录调节作用,并可能实现细胞周期控制和肿瘤抑制。