Nuclear protein phosphatase-1 regulates HIV-1 transcription
Nuclear protein phosphatase-1 regulates HIV-1 transcription
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DOI：
10.1074/jbc.m300521200
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发表时间：
2003-08-22
影响因子：
4.8
通讯作者：
Nekhai, S
中科院分区：
文献类型：
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作者：
Ammosova, T;Jerebtsova, M;Nekhai, S
我们最近报道了蛋白磷酸酶1 （PP1）在体外使RNA聚合酶II c末端重复序列去磷酸化并调节HIV-1转录。在这里，我们提供的证据表明，PP1也是tat诱导的HIV-1转录和培养细胞中的病毒复制所必需的。在瞬时转染实验中，通过过表达PP1核抑制剂（NIPP1）抑制PP1可抑制tat诱导的HIV-1转录。而与PP1结合缺陷的NIPP1突变体则没有这种效应。此外，pp1 γ的共表达逆转了NIPP1的抑制作用。腺相关病毒介导的NIPP1递送显著降低了表达tat的腺病毒在含有整合HIV-1启动子的CD4+ HeLa细胞（HeLa MAGI细胞）中诱导的HIV-1转录。此外，在感染HIV-1之前，用腺相关病毒nipp1感染HeLa MAGI细胞可显著降低HIV-1的复制水平。我们的结果表明PP1可能是HIV-1病毒转录所需的宿主细胞因子。因此，核PP1可能是抗hiv -1治疗的新靶点。
We recently reported that protein phosphatase 1 (PP1) dephosphorylates RNA polymerase II C-terminal repeats and regulates HIV-1 transcription in vitro. Here we provide evidence that PP1 is also required for Tat-induced HIV-1 transcription and for viral replication in cultured cells. Inhibition of PP1 by overexpression of nuclear inhibitor of PP1 (NIPP1) inhibited Tat-induced HIV-1 transcription in transient transfection assays. A mutant of NIPP1 that was defective in binding to PP1 did not have this effect. Also the co-expression of PP1gamma reversed the inhibitory effect of NIPP1. Adeno-associated virus-mediated delivery of NIPP1 significantly reduced HIV-1 transcription induced by Tat-expressing adenovirus in CD4+ HeLa cells that contained an integrated HIV-1 promoter ( HeLa MAGI cells). In addition, infection of HeLa MAGI cells with adeno-associated virus-NIPP1 prior to the infection with HIV-1 significantly reduced the level of HIV-1 replication. Our results indicate that PP1 might be a host cell factor that is required for HIV-1 viral transcription. Therefore, nuclear PP1 may represent a novel target for anti-HIV-1 therapeutics.