Overlapping functions of the pRb family in the regulation of rRNA synthesis
Overlapping functions of the pRb family in the regulation of rRNA synthesis
复制标题
DOI：
10.1128/mcb.21.17.5806-5814.2001
复制
发表时间：
2001-09-01
影响因子：
5.3
通讯作者：
White, RJ
中科院分区：
文献类型：
--
作者：
Ciarmatori, S;Scott, PH;White, RJ
“口袋”蛋白pRb、p107和p130是一个负生长调节蛋白家族。以前的研究表明，pRB的过表达可以抑制RNA聚合酶(Pol)I的转录。为了评估pRB在生理条件下是否发挥这一作用，我们检测了缺乏pRB或三种口袋蛋白组合的小鼠细胞中的前rRNA水平。在pRb基因敲除的成纤维细胞中，Pol I的转录没有受到影响，但对整个pRb家族的特异性干扰会解除对rRNA合成的调控。进一步分析表明，p130与pRb一样具有抑制Pol I转录的能力，而p107在该系统中不起作用。Rb-/-p130(-/-)成纤维细胞中rRNA的产生异常增加。此外，p130的过表达在体外和体内都可以抑制rRNA启动子。这反映了p130结合和失活上游结合因子UBF的能力。这些数据表明，活细胞中rRNA的合成受到内源性pRb和p130的多余控制。
The "pocket" proteins pRb, p107, and p130 are a family of negative growth regulators. Previous studies have demonstrated that overexpression of pRb can repress transcription by RNA polymerase (Pol) I. To assess whether pRb performs this role under physiological conditions, we have examined pre-rRNA levels in cells from mice lacking either pRb alone or combinations of the three pocket proteins. Pol I transcription was unaffected in pRb-knockout fibroblasts, but specific disruption of the entire pRb family deregulated rRNA synthesis. Further analysis showed that p130 shares with pRb the ability to repress Pol I transcription, whereas p107 is ineffective in this system. Production of rRNA is abnormally elevated in Rb-/- p130(-/-) fibroblasts. Furthermore, overexpression of p130 can inhibit an rRNA promoter both in vitro and in vivo. This reflects an ability of p130 to bind and inactivate the upstream binding factor, UBF. The data imply that rRNA synthesis in living cells is subject to redundant control by endogenous pRb and p130.