Felton-Edkins Zoë A, White Robert J
Institute of Biomedical and Life Sciences, Division of Biochemistry and Molecular Biology, Davidson Building, University of Glasgow, United Kingdom.
J Biol Chem. 2002 Dec 13;277(50):48182-91. doi: 10.1074/jbc.M201333200. Epub 2002 Oct 4.
RNA polymerase (pol) III transcription is abnormally active in fibroblasts transformed by polyomavirus (Py) or simian virus 40 (SV40). Several distinct mechanisms contribute to this effect. In untransformed fibroblasts, the basal pol III transcription factor (TF) IIIB is repressed through association with the retinoblastoma protein RB; this restraint is overcome by large T antigens of Py and SV40. Furthermore, cells transformed by these papovaviruses overexpress the BDP1 subunit of TFIIIB, at both the protein and mRNA levels. Despite the overexpression of BDP1, the abundance of the other TFIIIB components is unperturbed following papovavirus transformation. In contrast, mRNAs encoding all five subunits of the basal factor TFIIIC2 are found at elevated levels in fibroblasts transformed by Py or SV40. Thus, both papovaviruses stimulate pol III transcription by boosting production of selected components of the basal machinery. Py differs from SV40 in encoding a highly oncogenic middle T antigen that localizes outside the nucleus and activates several signal transduction pathways. Middle T can serve as a potent activator of a pol III reporter in transfected cells. Several distinct mechanisms therefore contribute to the high levels of pol III transcription that accompany transformation by Py and SV40.
在多瘤病毒（Py）或猿猴病毒40（SV40）转化的成纤维细胞中，RNA聚合酶（pol）III转录异常活跃。有几种不同的机制导致了这种效应。在未转化的成纤维细胞中，基础pol III转录因子（TF）IIIB通过与视网膜母细胞瘤蛋白RB结合而受到抑制；Py和SV40的大T抗原可克服这种抑制作用。此外，这些乳头瘤病毒转化的细胞在蛋白质和mRNA水平上均过表达TFIIIB的BDP1亚基。尽管BDP1过表达，但乳头瘤病毒转化后，TFIIIB其他组分的丰度并未受到干扰。相比之下，在Py或SV40转化的成纤维细胞中，基础因子TFIIIC2的所有五个亚基的mRNA水平均升高。因此，两种乳头瘤病毒都通过增加基础转录机制中特定组分的产生来刺激pol III转录。Py与SV40的不同之处在于，它编码一种高度致癌的中间T抗原，该抗原定位于细胞核外并激活多种信号转导途径。中间T可作为转染细胞中pol III报告基因的有效激活剂。因此，有几种不同的机制导致了Py和SV40转化时伴随的高水平pol III转录。
