Tat acetyl-acceptor lysines are important for human immunodeficiency virus type-1 replication
Tat acetyl-acceptor lysines are important for human immunodeficiency virus type-1 replication
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DOI：
10.1074/jbc.m201895200
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发表时间：
2002-06-21
影响因子：
4.8
通讯作者：
Benkirane, M
中科院分区：
文献类型：
--
作者：
Brès, V;Kiernan, R;Benkirane, M
人类免疫缺陷病毒1型反式激活因子达特是一种转录因子，通过与位于所有病毒转录物5 '端的反式激活应答区（TAR）结合来激活HIV-1启动子。我们和其他人最近已经表明，达特直接乙酰化赖氨酸28，在激活结构域，和赖氨酸50，在TAR RNA结合结构域，由塔特相关的组蛋白乙酰转移酶p300，p300/CBP相关因子，和hGCN 5。在这里，我们表明，突变的乙酰受体赖氨酸精氨酸或谷氨酰胺影响病毒复制。有趣的是，赖氨酸28和赖氨酸50的突变差异影响达特反式激活的整合与非整合的长末端重复。我们的研究结果突出了赖氨酸28和赖氨酸50的达特在病毒复制和塔特介导的反式激活的重要性。
The human immunodeficiency virus type-1 trans-activator Tat is a transcription factor that activates the HIV-1 promoter through binding to the trans-activation-responsive region (TAR) localized at the 5'-end of all viral transcripts. We and others have recently shown that Tat is directly acetylated at lysine 28, within the activation domain, and lysine 50, in the TAR RNA binding domain, by Tat-associated histone acetyltransferases p300, p300/CBP-associating factor, and hGCN5. Here, we show that mutation of acetyl-acceptor lysines to arginine or glutamine affects virus replication. Interestingly, mutation of lysine 28 and lysine 50 differentially affected Tat trans-activation of integrated versus nonintegrated long terminal repeat. Our results highlight the importance of lysine 28 and lysine 50 of Tat in virus replication and Tat-mediated trans-activation.