Dynamics of human immunodeficiency virus transcription: P-TEFb phosphorylates RD and dissociates negative effectors from the transactivation response element
Dynamics of human immunodeficiency virus transcription: P-TEFb phosphorylates RD and dissociates negative effectors from the transactivation response element
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DOI：
10.1128/mcb.24.2.787-795.2004
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发表时间：
2004-01-01
影响因子：
5.3
通讯作者：
Peterlin, BM
中科院分区：
文献类型：
--
作者：
Fujinaga, K;Irwin, D;Peterlin, BM
转录延伸是一个高度调控的过程，需要负效应和正效应。通过结合反式激活反应（TAR）元件中的双链茎，来自负转录延伸因子（NELF）的RD蛋白抑制来自人类免疫缺陷病毒1型（HIVLTR）长末端重复序列的基础转录。达特及其细胞辅因子，正转录延伸因子B（P-TEF B），克服了这种负面影响。P-TEFb中的Cdk 9也在其RNA识别基序旁边的位点磷酸化RD。一个突变的RD蛋白，模拟其磷酸化形式不再结合TAR，也不抑制HIV转录。与此形成鲜明对比的是，不能被P-TEFb磷酸化的突变RD蛋白作为显性负效应子发挥作用并抑制达特反式激活。这些结果更好地定义了从流产到生产性转录的转变，从而复制艾滋病毒。
The elongation of transcription is a highly regulated process that requires negative and positive effectors. By binding the double-stranded stem in the transactivation response (TAR) element, RD protein from the negative transcription elongation factor (NELF) inhibits basal transcription from the long terminal repeat of the human immunodeficiency virus type 1 (HIVLTR). Tat and its cellular cofactor, the positive transcription elongation factor b (P-TEFb), overcome this negative effect. Cdk9 in P-TEFb also phosphorylates RD at sites next to its RNA recognition motif. A mutant RD protein that mimics its phosphorylated form no longer binds TAR nor represses HIV transcription. In sharp contrast, a mutant RD protein that cannot be phosphorylated by P-TEFb functions as a dominant-negative effector and inhibits Tat transactivation. These results better define the transition from abortive to productive transcription and thus replication of HIV.