Yankulov K, Yamashita K, Roy R, Egly J M, Bentley D L
ICRF, London, United Kingdom.
J Biol Chem. 1995 Oct 13;270(41):23922-5. doi: 10.1074/jbc.270.41.23922.
Regulation of chain elongation by RNA polymerase II can have an important effect on gene expression (Bentley, D. (1995) Curr. Opin. Genet. Dev. 5, 210-216; Yankulov, K., Blau, J., Purton, T., Roberts, S., and Bentley, D. (1994) Cell 77, 749-759); however the mechanisms that control this step in transcription are not well understood. The adenosine analogue 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) has long been used as an inhibitor of RNA polymerase II elongation, but its target is not known. We show that DRB is a potent inhibitor of Cdk-activating kinase, associated with the general transcription factor TFIIH. Two other inhibitors of this kinase, H-7 and H-8, also inhibited transcriptional elongation. Furthermore, TFIIH kinase bound specifically to the herpes simplex virus VP16 activation domain which stimulates polymerase II elongation in addition to initiation (Yankulov, K., Blau, J., Purton, T., Roberts, S., and Bentley, D. (1994) Cell 77, 749-759). Our results suggest that DRB affects transcription by inhibiting the TFIIH-associated kinase and that this kinase functions in the control of elongation by RNA polymerase II.
RNA聚合酶II对链延伸的调控可对基因表达产生重要影响（本特利，D.（1995年）《当代遗传学发展观点》5，210 - 216；扬库洛夫，K.，布劳，J.，珀顿，T.，罗伯茨，S.，和本特利，D.（1994年）《细胞》77，749 - 759）；然而，控制转录这一步骤的机制尚未得到很好的理解。腺苷类似物5,6 - 二氯 - 1 - β - D - 呋喃核糖基苯并咪唑（DRB）长期以来一直被用作RNA聚合酶II延伸的抑制剂，但其靶点尚不清楚。我们发现DRB是一种与通用转录因子TFIIH相关的细胞周期蛋白依赖性激酶激活激酶的有效抑制剂。该激酶的另外两种抑制剂H - 7和H - 8也抑制转录延伸。此外，TFIIH激酶特异性结合单纯疱疹病毒VP16激活域，该激活域除了启动转录外还刺激聚合酶II延伸（扬库洛夫，K.，布劳，J.，珀顿，T.，罗伯茨，S.，和本特利，D.（1994年）《细胞》77，749 - 75）。我们的结果表明，DRB通过抑制与TFIIH相关的激酶来影响转录，并且该激酶在RNA聚合酶II延伸的控制中发挥作用。
