Suppression of HIV-1 transcriptional elongation by a DING phosphatase.
Suppression of HIV-1 transcriptional elongation by a DING phosphatase.
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DOI：
10.1002/jcb.22915
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发表时间：
2011-01
影响因子：
4
通讯作者：
Amini S
中科院分区：
文献类型：
--
作者：
Darbinian N;Gomberg R;Mullen L;Garcia S;White MK;Khalili K;Amini S
HIV-1基因转录受病毒和宿主因子的共同作用控制，这些因子与病毒启动子内跨越长末端重复序列（LTR）的特异性DNA序列结合。先前我们发现圣约翰草DING磷酸酶p27 SJ通过与病毒蛋白达特结合并阻止其核输入来抑制HIV-1基因转录。在这里，我们描述了抑制作用的p27 SJ对磷酸化的C-末端结构域（CTD）的RNA聚合酶II（RNAPII）。这种抑制导致RNAPII与LTR的结合受到抑制。通过p27 SJ抑制RNAPII与LTR的结合导致LTR转录延长的抑制和LTR转录活性的降低。另一种形式的圣约翰草DING磷酸酶p38 SJ也抑制RNAPII与LTR的结合，减少转录延伸，并且在抑制LTR的转录活性方面甚至比p27 SJ更强。我们的数据表明，p27 SJ/p38 SJ DING磷酸酶通过抑制RNAPII CTD的磷酸化和抑制LTR转录延长来调节HIV-1 LTR表达的可能机制。
HIV-1 gene transcription is controlled by the cooperation of viral and host factors which bind to specific DNA sequences within the viral promoter spanning the long terminal repeat, LTR. Previously we showed that the St. John's Wort DING phosphatase, p27SJ, suppresses HIV-1 gene transcription by binding to the viral protein Tat and preventing its nuclear import. Here, we describe the inhibitory effect of p27SJ on the phosphorylation of the C-terminal domain (CTD) of RNA polymerase II (RNAPII). This inhibition leads to the suppression of the association of RNAPII with the LTR. Inhibition of binding of RNAPII to LTR by p27SJ resulted in the suppression of LTR transcription elongation and a decrease in LTR transcriptional activity. Another form of the St. John's Wort DING phosphatase, p38SJ, also suppressed binding of RNAPII to the LTR, reduced transcription elongation and was even more powerful than p27SJ in inhibiting the transcriptional activity of the LTR. Our data suggest a possible mechanism by which the p27SJ/p38SJ DING phosphatase can regulate HIV-1 LTR expression by inhibiting phosphorylation of the CTD of RNAPII and suppressing LTR transcription elongation.