Zaborowska Justyna, Isa Nur F, Murphy Shona
Sir William Dunn School of Pathology University of Oxford Oxford UK.
Sir William Dunn School of Pathology University of Oxford Oxford UK; Department of Biotechnology Kulliyyah of Science, IIUM Kuantan Pahang Malaysia.
Inside Cell. 2016 Apr;1(2):106-116. doi: 10.1002/icl3.1037. Epub 2015 Nov 25.
Positive transcription elongation factor b (P-TEFb), which comprises cyclin-dependent kinase 9 (CDK9) kinase and cyclin T subunits, is an essential kinase complex in human cells. Phosphorylation of the negative elongation factors by P-TEFb is required for productive elongation of transcription of protein-coding genes by RNA polymerase II (pol II). In addition, P-TEFb-mediated phosphorylation of the carboxyl-terminal domain (CTD) of the largest subunit of pol II mediates the recruitment of transcription and RNA processing factors during the transcription cycle. CDK9 also phosphorylates p53, a tumor suppressor that plays a central role in cellular responses to a range of stress factors. Many viral factors affect transcription by recruiting or modulating the activity of CDK9. In this review, we will focus on how the function of CDK9 is regulated by viral gene products. The central role of CDK9 in viral life cycles suggests that drugs targeting the interaction between viral products and P-TEFb could be effective anti-viral agents.
正性转录延伸因子b（P-TEFb）由细胞周期蛋白依赖性激酶9（CDK9）和细胞周期蛋白T亚基组成，是人体细胞中一种重要的激酶复合物。P-TEFb对负性延伸因子的磷酸化作用是RNA聚合酶II（pol II）有效延伸蛋白质编码基因转录所必需的。此外，P-TEFb介导的pol II最大亚基羧基末端结构域（CTD）的磷酸化作用在转录周期中介导转录和RNA加工因子的募集。CDK9还可磷酸化p53，p53是一种肿瘤抑制因子，在细胞对一系列应激因子的反应中起核心作用。许多病毒因子通过募集或调节CDK9的活性来影响转录。在本综述中，我们将重点关注CDK9的功能是如何被病毒基因产物调控的。CDK9在病毒生命周期中的核心作用表明，靶向病毒产物与P-TEFb之间相互作用的药物可能是有效的抗病毒药物。
