Multiple mechanisms contribute to the activation of RNA polymerase III transcription in cells transformed by papovaviruses
Multiple mechanisms contribute to the activation of RNA polymerase III transcription in cells transformed by papovaviruses
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DOI：
10.1074/jbc.m201333200
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发表时间：
2002-12-13
影响因子：
4.8
通讯作者：
White, RJ
中科院分区：
文献类型：
--
作者：
Felton-Edkins, ZA;White, RJ
RNA 聚合酶 (pol) III 转录在多瘤病毒 (Py) 或猿猴病毒 40 (SV40) 转化的成纤维细胞中异常活跃。有几种不同的机制促成了这种效果。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 抗原克服了这种限制。此外，被这些乳多空病毒转化的细胞在蛋白质和 mRNA 水平上过度表达 TFIIIB 的 BDP1 亚基。尽管 BDP1 过度表达，但其他 TFIIIB 成分的丰度在乳多空病毒转化后并未受到干扰。相比之下，在 Py 或 SV40 转化的成纤维细胞中，编码基础因子 TFIIIC2 所有五个亚基的 mRNA 水平升高。因此，两种乳多空病毒都通过促进基础机器选定组件的产生来刺激 pol III 转录。 Py 与 SV40 的不同之处在于编码一种高度致癌的中间 T 抗原，该抗原位于细胞核外并激活多个信号转导途径。 Middle T 可作为转染细胞中 pol III 报告基因的有效激活剂。因此，几种不同的机制有助于伴随 Py 和 SV40 转化的高水平 pol III 转录。
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.