Regulation of Tat Acetylation and Transactivation Activity by the Microtubule-associated Deacetylase HDAC6
Regulation of Tat Acetylation and Transactivation Activity by the Microtubule-associated Deacetylase HDAC6
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微管相关脱乙酰酶 HDAC6 对 Tat 乙酰化和反式激活活性的调节
DOI：
10.1074/jbc.m110.208884
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发表时间：
2011-03-18
影响因子：
4.8
通讯作者：
Zhou, Jun
中科院分区：
文献类型：
--
作者：
Huo, Lihong;Li, Dengwen;Zhou, Jun
达特的可逆乙酰化是其对HIV-1转录的反式激活活性的关键。然而，参与乙酰化/脱乙酰化循环的酶尚未完全表征。本研究通过酵母双杂交技术，发现组蛋白去乙酰化酶HDAC 6是达特的结合伴侣。我们的数据表明，HDAC 6与达特在细胞质中以微管依赖性方式相互作用。此外，HDAC 6在Lys-28处使达特脱乙酰基，从而抑制Tat介导的HIV-1启动子的反式激活。HDAC 6的失活促进了达特与细胞周期蛋白T1的相互作用，并导致达特反式激活活性的增加。这些发现确立了HDAC 6作为达特脱乙酰酶，并支持了一个模型，其中Lys-28脱乙酰化通过影响达特与细胞周期蛋白T1和反式激活应答RNA形成核糖核蛋白复合物的能力来降低达特反式激活活性。
Reversible acetylation of Tat is critical for its transactivation activity toward HIV-1 transcription. However, the enzymes involved in the acetylation/deacetylation cycles have not been fully characterized. In this study, by yeast two-hybrid assay, we have discovered the histone deacetylase HDAC6 to be a binding partner of Tat. Our data show that HDAC6 interacts with Tat in the cytoplasm in a microtubule-dependent manner. In addition, HDAC6 deacetylates Tat at Lys-28 and thereby suppresses Tat-mediated transactivation of the HIV-1 promoter. Inactivation of HDAC6 promotes the interaction of Tat with cyclin T1 and leads to an increase in Tat transactivation activity. These findings establish HDAC6 as a Tat deacetylase and support a model in which Lys-28 deacetylation decreases Tat transactivation activity through affecting the ability of Tat to form a ribonucleoprotein complex with cyclin T1 and the transactivation-responsive RNA.