A protein phosphatase from human T cells augments Tat transactivation of the human immunodeficiency virus type 1 long-terminal repeat
A protein phosphatase from human T cells augments Tat transactivation of the human immunodeficiency virus type 1 long-terminal repeat
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DOI：
10.1006/viro.2002.1438
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发表时间：
2002-04-25
期刊：
影响因子：
3.7
通讯作者：
Kumar, A
中科院分区：
文献类型：
--
作者：
Bharucha, DC;Zhou, MS;Kumar, A
HIV-1达特蛋白通过调节细胞转录因子与RNA聚合酶II（RNAPII）的活性和结合来调节病毒基因表达。可能的机制包括调节RNAPII大亚基C-末端结构域（CTD）磷酸化的Tat相关蛋白激酶和磷酸酶。低磷酸化的RNAPII（RNAPIIa）在前起始复合物形成期间被募集到启动子，而高磷酸化的RNAPII（RNAPIIo）与延伸复合物相关。磷酸酶在维持RNAPII的两种磷酸化状态之间的平衡中的作用尚不清楚，这是HIV-1 LTR持续转录激活所需的。在这项研究中，我们讨论了从Jurkat T细胞中分离的Tat相关CTD磷酸酶的性质。Tat相关蛋白磷酸酶（TAPP）与丝氨酸/苏氨酸1型蛋白磷酸酶（PP 1）家族相关。TAPP特异性地在丝氨酸2上使重组CTD的过度磷酸化形式去磷酸化，并在体外转录反应中增强Tat介导的HIV-1 LTR的转录反式激活。TAPP在早期起始步骤中与转录复合物相关，并且其从HIV-1启动子的释放与CDK 9的Tat特异性激活一致。结果表明Tat相关磷酸酶的独特作用，其在延伸的早期阶段通过RNAPIl的靶向特异性去磷酸化来调节病毒转录。(C)2002 Elsevier Science（美国）。
HIV-1 Tat protein regulates viral gene expression by modulating the activity and association of cellular transcription factors with RNA polymerase II (RNAPII). Possible mechanisms include Tat-associated protein kinase(s) and phosphatase(s) that regulate phosphorylation of the C-terminal domain (CTD) of the large subunit of RNAPII Hypophosphorylated RNAPII (RNAPIIa) is recruited to promoters during formation of a preinitiation complex, whereas hyperphosphorylated RNAPII (RNAPIIo) is associated with the elongation complex. The role of phosphatases in maintaining the equilibrium between the two phosphorylated states of RNAPII, which is required for sustained transcriptional activation from the HIV-1 LTR, is not clear. In this study, we discuss the properties of a Tat-associated CTD phosphatase fractionated from Jurkat T cells. The Tat-associated protein phosphatase (TAPP) is related to the serine/threonine, type 1, protein phosphatase (PP1) family. TAPP dephosphorylates the hyperphosphorylated form of recombinant CTD specifically on serine 2, and augments Tat-mediated transcriptional transactivation of HIV-1 LTR in an in vitro transcription reaction. TAPP is associated with the transcription complex during the early initiation steps, and its release from the HIV-1 promoter coincides with the Tat-specific activation of CDK9. The results suggest a unique role of the Tat-associated phosphatase which regulates viral transcription by target-specific dephosphorylation of RNAPIl during the early stages of elongation. (C) 2002 Elsevier Science (USA).