Acetylation of Tat defines a CyclinT1-independent step in HIV transactivation
Acetylation of Tat defines a CyclinT1-independent step in HIV transactivation
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DOI：
10.1016/s1097-2765(03)00245-4
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发表时间：
2003-07-01
期刊：
影响因子：
16
通讯作者：
Ott, M
中科院分区：
文献类型：
--
作者：
Kaehlcke, K;Dorr, A;Ott, M
HIV转录激活因子达特在TAR RNA结合结构域中的单个赖氨酸残基处被p300乙酰化。我们已经产生了对乙酰化形式的达特（Ac达特）具有特异性的单克隆和多克隆抗体。显微注射抗AcTat抗体抑制细胞中Tat介导的反式激活。类似地，p300抑制剂Lys-CoA和p300特异性siRNA抑制了达特转录活性。全长合成的Ac达特与TAR RNA结合的亲和力与未乙酰化的达特相同，但在Ac达特存在下，Tat-TAR-CyclinT 1三元复合物的形成被完全抑制。我们认为达特乙酰化可能有助于达特辅因子CyclinT 1从TAR RNA中解离，并将达特转移到延伸RNA聚合酶II上。
The HIV transcriptional activator Tat is acetylated by p300 at a single lysine residue in the TAR RNA binding domain. We have generated monoclonal and polyclonal antibodies specific for the acetylated form of Tat (AcTat). Microinjection of anti-AcTat antibodies inhibited Tat-mediated transactivation in cells. Similarly, the p300 inhibitor Lys-CoA and siRNA specific for p300 suppressed Tat transcriptional activity. Full-length synthetic AcTat bound to TAR RNA with the same affinity as unacetylated Tat, but formation of a Tat-TAR-CyclinT1 ternary complex was completely inhibited in the presence of AcTat. We propose that Tat acetylation may help in dissociating the Tat cofactor CyclinT1 from TAR RNA and serve to transfer Tat onto the elongating RNA polymerase II.