Protein kinase D3 is essential for prostratin-activated transcription of integrated HIV-1 provirus promoter via NF-κB signaling pathway.
Protein kinase D3 is essential for prostratin-activated transcription of integrated HIV-1 provirus promoter via NF-κB signaling pathway.
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DOI：
10.1155/2014/968027
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发表时间：
2014
影响因子：
--
通讯作者：
Liu R
中科院分区：
文献类型：
--
作者：
Wang H;Zhu X;Zhu Y;Liu J;Hu X;Wang Y;Peng S;Chen Y;Chen R;Ding F;Liu R
Prostratin被认为是一种通过诱导HIV-1转录激活来消除潜伏的HIV-1前病毒的有前途的试剂。然而，这种激活的分子机制还远不清楚。在这里，我们表明，蛋白激酶D3（PKD 3）是必不可少的前列腺素诱导的转录激活潜伏的HIV-1前病毒。首先，沉默PKD 3，而不是PKD家族的其他成员，阻断了前列腺素诱导的HIV-1转录。第二，过度表达PKD 3的组成型活性形式，而不是PKD 3的野生型或激酶死亡形式，增加了HIV-1的表达。与这一观察结果一致，我们发现prostratin可以通过诱导其激活环的磷酸化来触发PKD 3激活。此外，我们确定了新的PKC亚家族的PKCε作为这种磷酸化的上游激酶。最后，PKD 3对HIV-1转录的激活作用被证明依赖于κB元件的存在和prostratin诱导的NF-κB的激活，如通过沉默PKD 3阻断prostratin诱导的NF-κB激活和NF-κ B依赖的HIV-1转录的事实所表明的。因此，首次发现PKD 3参与了潜伏的HIV-1前病毒的转录激活，揭示了前列腺素通过PKCε/PKD 3/NF-κB信号通路诱导HIV-1转录的分子机制。
Prostratin has been proposed as a promising reagent for eradicating the latent HIV-1 provirus by inducing HIV-1 transcription activation. The molecular mechanism of this activation, however, is far from clear. Here, we show that the protein kinase D3 (PKD3) is essential for prostratin-induced transcription activation of latent HIV-1 provirus. First, silencing PKD3, but not the other members of PKD family, blocked prostratin-induced transcription of HIV-1. Second, overexpressing the constitutively active form of PKD3, but not the wild-type or kinase-dead form of PKD3, augmented the expression of HIV-1. Consistent with this observation, we found that prostratin could trigger PKD3 activation by inducing the phosphorylation of its activation loop. In addition, we identified PKCε of the novel PKC subfamily as the upstream kinase for this phosphorylation. Finally, the activation effect of PKD3 on HIV-1 transcription was shown to depend on the presence of κB element and the prostratin-induced activation of NF-κB, as indicated by the fact that silencing PKD3 blocked prostratin-induced NF-κB activation and NF-κB-dependent HIV-1 transcription. Therefore, for the first time, PKD3 is implicated in the transcription activation of latent HIV-1 provirus, and our results revealed a molecular mechanism of prostratin-induced HIV-1 transcription via PKCε/PKD3/NF-κB signaling pathway.
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影响因子：
4.8
作者：
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通讯作者：
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DOI：
10.1016/j.bbrc.2006.02.013
发表时间：
2006-04-14
影响因子：
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