NUCKS1, a novel Tat coactivator, plays a crucial role in HIV-1 replication by increasing Tat-mediated viral transcription on the HIV-1 LTR promoter.
NUCKS1, a novel Tat coactivator, plays a crucial role in HIV-1 replication by increasing Tat-mediated viral transcription on the HIV-1 LTR promoter.
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DOI：
10.1186/s12977-014-0067-y
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发表时间：
2014-08-13
期刊：
影响因子：
3.3
通讯作者：
Yoon CH
中科院分区：
文献类型：
--
作者：
Kim HY;Choi BS;Kim SS;Roh TY;Park J;Yoon CH
人类免疫缺陷病毒-1 (HIV-1) Tat蛋白在HIV-1长末端重复（LTR）转录和复制过程中起着重要作用。Tat的转录活性受多种宿主因子的调控，但宿主因子调控Tat的机制尚不清楚。利用酵母双杂交筛选系统，我们鉴定出核泛在酪蛋白和周期蛋白依赖性激酶底物1 （NUCKS1）作为一种新的tata相互作用伙伴。在这里，我们报告了它作为Tat的正调节器的功能。在共免疫沉淀实验中，HIV-1 Tat与内源性和异位表达的NUCKS1充分相互作用。在报告基因实验中，异位表达NUCKS1显著增加了Tat介导的HIV-1 LTR转录，而小干扰RNA敲低NUCKS1则会减少Tat介导的HIV-1 LTR转录。我们还研究了NUCKS1介导Tat激活的机制。在染色质免疫沉淀试验（ChIP）中，敲低NUCKS1阻断了LTR上交易激活反应（TAR）区域Tat的积累，从而导致病毒复制受到抑制。然而，NUCKS1的表达并没有增加Tat核定位和与Cyclin T1的相互作用。有趣的是，潜伏hiv -1感染细胞中的NUCKS1表达水平低于未感染的亲本细胞。此外，NUCKS1的表达水平被显著诱导，从而促进HIV-1在潜伏感染细胞中的再激活。综上所述，我们的数据清楚地表明NUCKS1是Tat介导的HIV-1转录和复制所必需的一种新型Tat共激活子，并且它可能有助于潜伏HIV-1感染细胞中的HIV-1再激活。本文的在线版本（doi:10.1186/s12977-014-0067-y）包含补充材料，可供授权用户使用。
Human immunodeficiency virus-1 (HIV-1) Tat protein plays an essential role in HIV gene transcription from the HIV-1 long terminal repeat (LTR) and replication. Transcriptional activity of Tat is modulated by several host factors, but the mechanism responsible for Tat regulation by host factors is not understood fully. Using a yeast two-hybrid screening system, we identified Nuclear ubiquitous casein and cyclin-dependent kinase substrate 1 (NUCKS1) as a novel Tat-interacting partner. Here, we report its function as a positive regulator of Tat. In a coimmunoprecipitation assay, HIV-1 Tat interacted sufficiently with both endogenous and ectopically expressed NUCKS1. In a reporter assay, ectopic expression of NUCKS1 significantly increased Tat-mediated transcription of the HIV-1 LTR, whereas knockdown of NUCKS1 by small interfering RNA diminished Tat-mediated transcription of the HIV-1 LTR. We also investigated which mechanism contributes to NUCKS1-mediated Tat activation. In a chromatin immunoprecipitation assay (ChIP), knockdown of NUCKS1 interrupted the accumulation of Tat in the transactivation-responsive (TAR) region on the LTR, which then led to suppression of viral replication. However, NUCKS1 expression did not increase Tat nuclear localization and interaction with Cyclin T1. Interestingly, the NUCKS1 expression level was lower in latently HIV-1-infected cells than in uninfected parent cells. Besides, expression level of NUCKS1 was markedly induced, which then facilitated HIV-1 reactivation in latently infected cells. Taken together, our data demonstrate clearly that NUCKS1 is a novel Tat coactivator that is required for Tat-mediated HIV-1 transcription and replication, and that it may contribute to HIV-1 reactivation in latently HIV-1 infected cells. The online version of this article (doi:10.1186/s12977-014-0067-y) contains supplementary material, which is available to authorized users.
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影响因子：
16
作者：
He N;Liu M;Hsu J;Xue Y;Chou S;Burlingame A;Krogan NJ;Alber T;Zhou Q
通讯作者：
Zhou Q
影响因子：
6.7
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Lesbats P;Botbol Y;Chevereau G;Vaillant C;Calmels C;Arneodo A;Andreola ML;Lavigne M;Parissi V
通讯作者：
Parissi V
影响因子：
10.5
作者：
Li, XY;Green, MR
通讯作者：
Green, MR
影响因子：
4.8
作者：
Holloway, AF;Occhiodoro, F;Shannon, MF
通讯作者：
Shannon, MF
影响因子：
5.4
作者：
Friedman, Julia;Cho, Won-Kyung;Karn, Jonathan
通讯作者：
Karn, Jonathan