Control of the histone-acetyltransferase activity of Tip60 by the HIV-1 transactivator protein, Tat
Control of the histone-acetyltransferase activity of Tip60 by the HIV-1 transactivator protein, Tat
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DOI：
10.1021/bi9907274
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发表时间：
1999-07-06
期刊：
影响因子：
2.9
通讯作者：
Khochbin, S
中科院分区：
文献类型：
--
作者：
Creaven, M;Hans, F;Khochbin, S
Tip 60是一种细胞组蛋白乙酰转移酶，已知其与HIV-1编码的反式激活蛋白达特相互作用。在这项工作中，我们表明，焦油与Tip 60的相互作用有效地抑制Tip 60组蛋白乙酰转移酶的活性。Tip 60除了具有组蛋白乙酰转移酶活性外，还可以进行不受达特相互作用影响的自乙酰化。我们的数据表明，Tip 60不显着影响Tat依赖的转录激活的S-LTR的HIV，这表明它与达特的相互作用影响相同的内在细胞过程。然后，我们能够确定一个细胞基因，锰依赖性超氧化物歧化酶（Mn-SOD），具有Tip 60依赖的转录活性。有趣的是，同时表达达特和Tip 60消除了Tip 60对Mn-SOD启动子活性的影响。我们推测HIV-1反式激活因子达特在靶向Tip 60时阻碍了细胞基因（如Mn-SOD）的表达，这些基因通常会干扰病毒的有效复制和繁殖。
Tip60, a cellular histone-acetyltransferase, is known to interact with the HIV-1-encoded transactivator protein, Tat. In this work, we show that the interaction of Tar with Tip60 efficiently inhibits the Tip60 histone-acetyltransferase activity. Besides its histone-acetyltransferase activity, Tip60 can undergo an autoacetylation which is not affected by Tat interaction. Our data show that Tip60 does not significantly influence Tat-dependent transcriptional activation of the S-LTR of HIV, suggesting that its interaction with Tat affects same intrinsic cellular process. We were then able to identify a cellular gene, Mn-dependent superoxide dismutase (Mn-SOD);that has a Tip60-dependent transcriptional activity. Interestingly, the simultaneous expression of Tat and Tip60 abolishes the effect of Tip60 on the activity of the Mn-SOD promoter. We postulate that the HIV-1 transactivator, Tat, in targeting Tip60 hinders the expression of cellular genes (such as Mn-SOD) which normally interfere with the efficient replication and propagation of the virus.