The histone acetyltransferase, hGCN5, interacts with and acetylates the HIV transactivator, Tat
The histone acetyltransferase, hGCN5, interacts with and acetylates the HIV transactivator, Tat
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DOI：
10.1074/jbc.m101385200
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发表时间：
2001-07-27
影响因子：
4.8
通讯作者：
Khochbin, S
中科院分区：
文献类型：
--
作者：
Col, E;Caron, C;Khochbin, S
与几种组蛋白乙酰转移酶相关的因子乙酰转移酶活性在转录控制中起关键作用。在此我们报道，一种众所周知的组蛋白乙酰转移酶hGCN5与人类免疫缺陷病毒1型（HIV - 1）反式激活蛋白Tat特异性相互作用并使其乙酰化。Tat和hGCN5之间的相互作用是直接的，涉及hGCN5的乙酰转移酶和溴结构域区域，以及包含Tat蛋白富含半胱氨酸结构域的一个有限区域。Tat的赖氨酸50和51是p300/CBP乙酰化的靶点，也被发现可被hGCN5乙酰化。最近已表明p300/CBP对这两个赖氨酸的乙酰化可刺激Tat的转录活性，相应地，我们发现hGCN5可显著增强HIV - 1长末端重复序列的Tat依赖性转录。这些数据强调了赖氨酸50和51的乙酰化在Tat功能中的重要性，因为参与不同信号通路的不同组蛋白乙酰转移酶，即GCN5和p300/CBP，汇聚在同一位点使Tat乙酰化。
Factor acetyltransferase activity associated with several histone acetyltransferases plays a key role in the control of transcription. Here we report that hGCN5, a well known histone acetyltransferase, specifically interacts with and acetylates the human immunodeficiency virus type 1 (HIV-1) transactivator protein, Tat. The interaction between Tat and hGCN5 is direct and involves the acetyltransferase and the bromodomain regions of hGCN5, as well as a limited region of Tat encompassing the cysteine-rich domain of the protein. Tat lysines 50 and 51, target of acetylation by p300/CBP, were also found to be acetylated by hGCN5. The acetylation of these two lysines by p300/CBP has been recently shown to stimulate Tat transcriptional activity and accordingly, we have found that hGCN5 can considerably enhance Tat-dependent transcription of the HIV-1 long terminal repeat. These data highlight the importance of the acetylation of lysines 50 and 51 in the function of Tat, since different histone acetyltransferases involved in distinct signaling pathways, GCN5 and p300/CBP, converge to acetylate Tat on the same site.