Scott P H, Cairns C A, Sutcliffe J E, Alzuherri H M, McLees A, Winter A G, White R J
Institute of Biomedical and Life Sciences, Division of Biochemistry and Molecular Biology, University of Glasgow, Glasgow G12 8QQ, United Kingdom.
J Biol Chem. 2001 Jan 12;276(2):1005-14. doi: 10.1074/jbc.M005417200.
Increased rates of RNA polymerase (pol) III transcription constitute a central feature of the mitogenic response, but little is known about the mechanism(s) responsible. We demonstrate that the retinoblastoma protein RB plays a major role in suppressing pol III transcription in growth-arrested fibroblasts. RB knockout cells are compromised in their ability to down-regulate pol III following serum withdrawal. RB binds and represses the pol III-specific transcription factor TFIIIB during G(0) and early G(1), but this interaction decreases as cells approach S phase. Full induction of pol III coincides with mid- to late G(1) phase, when RB becomes phosphorylated by cyclin D- and E-dependent kinases. TFIIIB only associates with the underphosphorylated form of RB, and overexpression of cyclins D and E stimulates pol III transcription in vivo. The RB-related protein p130 also contributes to the repression of TFIIIB in growth-arrested fibroblasts. These observations provide insight into the mechanisms responsible for controlling pol III transcription during the switch between growth and quiescence.
RNA聚合酶（pol）III转录速率的增加是有丝分裂原反应的一个核心特征，但对于其相关机制却知之甚少。我们证明，视网膜母细胞瘤蛋白RB在抑制生长停滞的成纤维细胞中的pol III转录中起主要作用。RB基因敲除细胞在血清撤出后下调pol III的能力受损。在G(0)期和早期G(1)期，RB结合并抑制pol III特异性转录因子TFIIIB，但随着细胞接近S期，这种相互作用会减弱。pol III的完全诱导与G(1)期中期至晚期一致，此时RB被细胞周期蛋白D和E依赖性激酶磷酸化。TFIIIB仅与未磷酸化形式的RB结合，并且细胞周期蛋白D和E的过表达在体内刺激pol III转录。RB相关蛋白p130也有助于在生长停滞的成纤维细胞中抑制TFIIIB。这些观察结果为在生长和静止之间转换期间控制pol III转录的机制提供了见解。
