Brown T R, Scott P H, Stein T, Winter A G, White R J
Institute of Biomedical and Life Sciences, Division of Biochemistry and Molecular Biology, University of Glasgow, UK.
Gene Expr. 2000;9(1-2):15-28. doi: 10.3727/000000001783992713.
The level of RNA polymerase (pol) III transcription is tightly linked to the rate of growth; it is low in resting cells and increases following mitogenic stimulation. When mammalian cells begin to proliferate, maximal pol III activity is reached shortly before the G1/S transition; it then remains high throughout S and G2 phases. Recent data suggest that the retinoblastoma protein RB and its relatives p107 and p130 may be largely responsible for this pattern of expression. During G0 and early G1 phase, RB and p130 bind and repress the pol III-specific factor TFIIIB; shortly before S phase they dissociate from TFIIIB, allowing transcription to increase. At the end of interphase, when cells enter mitosis, pol III transcription is again suppressed; this mitotic repression is achieved through direct phosphorylation of TFIIIB. Thus, pol III transcription levels fluctuate as mammalian cells cycle, being high in S and G2 phases and low during mitosis and early G1. In addition to this cyclic regulation, TFIIIB can be bound and repressed by the tumor suppressor p53. Conversely, it is a target for activation by several viruses, including SV40, HBV, and HTLV-1. Some viruses also increase the activity of a second pol III-specific factor called TFIIIC. A large proportion of transformed and tumor cell types express abnormally high levels of pol III products. This may be explained, at least in part, by the very high frequency with which RB and p53 become inactivated during neoplastic transformation; loss of function of these cardinal tumor suppressors may release TFIIIB from key restraints that operate in normal cells.
RNA聚合酶（pol）III的转录水平与细胞生长速率紧密相关；在静止细胞中其水平较低，有丝分裂原刺激后则升高。当哺乳动物细胞开始增殖时，在G1/S转换前不久达到最大的pol III活性；然后在整个S期和G2期保持较高水平。最近的数据表明，视网膜母细胞瘤蛋白RB及其相关蛋白p107和p130可能在很大程度上决定了这种表达模式。在G0期和G1早期，RB和p130结合并抑制pol III特异性因子TFIIIB；在S期前不久它们与TFIIIB解离，从而使转录增加。在间期结束时，当细胞进入有丝分裂时，pol III转录再次受到抑制；这种有丝分裂抑制是通过TFIIIB的直接磷酸化实现的。因此，随着哺乳动物细胞周期的进行，pol III转录水平会发生波动，在S期和G2期较高，而在有丝分裂期和G1早期较低。除了这种周期性调节外，肿瘤抑制因子p53可以结合并抑制TFIIIB。相反，它是包括SV40、HBV和HTLV-1在内的几种病毒的激活靶点。一些病毒还会增加另一种称为TFIIIC的pol III特异性因子的活性。很大一部分转化细胞和肿瘤细胞类型表达异常高水平的pol III产物。这至少部分可以解释为，在肿瘤转化过程中RB和p53失活的频率非常高；这些主要肿瘤抑制因子的功能丧失可能会使TFIIIB从正常细胞中起作用的关键抑制中释放出来。
