包含Tat和细胞周期蛋白T1的蛋白质复合物被招募至TAR决定了HIV-1 Tat的物种特异性。
Recruitment of a protein complex containing Tat and cyclin T1 to TAR governs the species specificity of HIV-1 Tat.
作者信息
Bieniasz P D, Grdina T A, Bogerd H P, Cullen B R
机构信息
Howard Hughes Medical Institute and Department of Genetics, Box 3025, Room 426, CARL Building, Duke University Medical Center, Research Drive, Durham, NC 27710, USA.
出版信息
EMBO J. 1998 Dec 1;17(23):7056-65. doi: 10.1093/emboj/17.23.7056.
Abstract
Human cyclin T1 (hCycT1), a major subunit of the essential elongation factor P-TEFb, has been proposed to act as a cofactor for human immunodeficiency virus type 1 (HIV-1) Tat. Here, we show that murine cyclin T1 (mCycT1) binds the activation domain of HIV-1 Tat but, unlike hCycT1, cannot mediate Tat function because it cannot be recruited efficiently to TAR. In fact, overexpression of mCycT1, but not hCycT1, specifically inhibits Tat-TAR function in human cells. This discordant phenotype results from a single amino acid difference between hCycT1 and mCycT1, a tyrosine in place of a cysteine at residue 261. These data indicate that the ability of Tat to recruit CycT1/P-TEFb to TAR determines the species restriction of HIV-1 Tat function in murine cells and therefore demonstrate that this recruitment is a critical function of the Tat protein.
摘要
人细胞周期蛋白T1（hCycT1）是必需延伸因子P-TEFb的主要亚基，被认为可作为1型人类免疫缺陷病毒（HIV-1）反式激活因子（Tat）的辅助因子。在此，我们发现小鼠细胞周期蛋白T1（mCycT1）能结合HIV-1 Tat的激活结构域，但与hCycT1不同，它不能介导Tat功能，因为它不能有效地被募集到TAR。事实上，mCycT1（而非hCycT1）的过表达会特异性抑制人类细胞中的Tat-TAR功能。这种不一致的表型源于hCycT1和mCycT1之间的单个氨基酸差异，即第261位残基处的酪氨酸取代了半胱氨酸。这些数据表明，Tat将CycT1/P-TEFb募集到TAR的能力决定了HIV-1 Tat功能在小鼠细胞中的物种限制，因此证明这种募集是Tat蛋白的关键功能。
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本文引用的文献
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Transcription elongation factor P-TEFb mediates Tat activation of HIV-1 transcription at multiple stages.转录延伸因子P-TEFb在多个阶段介导Tat对HIV-1转录的激活作用。
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HIV-1 auxiliary proteins: making connections in a dying cell.HIV-1辅助蛋白：在濒死细胞中建立联系
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PITALRE, the catalytic subunit of TAK, is required for human immunodeficiency virus Tat transactivation in vivo.TAK的催化亚基PITALRE在体内是人类免疫缺陷病毒Tat反式激活所必需的。
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A novel CDK9-associated C-type cyclin interacts directly with HIV-1 Tat and mediates its high-affinity, loop-specific binding to TAR RNA.一种新型的与CDK9相关的C型细胞周期蛋白直接与HIV-1反式激活因子（Tat）相互作用，并介导其与TAR RNA的高亲和力、环特异性结合。
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A cofactor, TIP30, specifically enhances HIV-1 Tat-activated transcription.一种辅助因子TIP30特异性增强HIV-1反式激活因子（Tat）激活的转录。
Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2146-51. doi: 10.1073/pnas.95.5.2146.
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TAK, an HIV Tat-associated kinase, is a member of the cyclin-dependent family of protein kinases and is induced by activation of peripheral blood lymphocytes and differentiation of promonocytic cell lines.TAK是一种与HIV反式激活因子（Tat）相关的激酶，属于细胞周期蛋白依赖性蛋白激酶家族成员，可通过外周血淋巴细胞激活和原单核细胞系分化诱导产生。
Proc Natl Acad Sci U S A. 1997 Nov 11;94(23):12331-6. doi: 10.1073/pnas.94.23.12331.
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The HIV transactivator TAT binds to the CDK-activating kinase and activates the phosphorylation of the carboxy-terminal domain of RNA polymerase II.HIV反式激活因子TAT与细胞周期蛋白依赖性激酶激活激酶结合，并激活RNA聚合酶II羧基末端结构域的磷酸化。
Genes Dev. 1997 Oct 15;11(20):2645-57. doi: 10.1101/gad.11.20.2645.
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P-TEFb kinase is required for HIV Tat transcriptional activation in vivo and in vitro.P-TEFb激酶在体内和体外对于HIV Tat转录激活都是必需的。
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