Differential acetylation of Tat coordinates its interaction with the co-activators cyclin T1 and PCAF
Differential acetylation of Tat coordinates its interaction with the co-activators cyclin T1 and PCAF
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DOI：
10.1093/emboj/cdf669
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发表时间：
2002-12-16
期刊：
影响因子：
11.4
通讯作者：
Kiernan, RE
中科院分区：
文献类型：
--
作者：
Brès, V;Tagami, H;Kiernan, RE
HIV-1反式激活蛋白，达特，是一种非典型的转录激活因子，通过结合短的前导RNA，TAR而不是DNA发挥作用。虽然其功能机制的细节仍然是未知的，新的研究结果表明，达特主要用于适应共激活复合物，如p300，PCAF和P-TEFb的HIV-1长末端重复。因此，了解达特如何与这些辅因子相互作用是至关重要的。最近研究表明，单个赖氨酸（残基50）的乙酰化调节达特与PCAF的结合。在这里，我们报告说，在没有达特乙酰化，PCAF结合氨基酸20 - 40内的达特。有趣的是，达特在Lys28处的乙酰化消除了Tat-PCAF相互作用。在Lys50处的乙酰化产生了用于结合PCAF的新位点，并决定了Tat-PCAF-P-TEFb的三元复合物的形成。因此，差异赖氨酸乙酰化的达特协调与其共激活剂，细胞周期蛋白T1和PCAF的相互作用。我们的研究结果可能有助于理解达特共激活剂的HIV-1启动子的有序招募。
The HIV-1 transactivator protein, Tat, is an atypical transcriptional activator that functions through binding, not to DNA, but to a short leader RNA, TAR. Although details of its functional mechanism are still unknown, emerging findings suggest that Tat serves primarily to adapt co-activator complexes such as p300, PCAF and P-TEFb to the HIV-1 long terminal repeat. Hence, an understanding of how Tat interacts with these cofactors is crucial. It has recently been shown that acetylation at a single lysine, residue 50, regulated the association of Tat with PCAF. Here, we report that in the absence of Tat acetylation, PCAF binds to amino acids 20-40 within Tat. Interestingly, acetylation of Tat at Lys28 abrogates Tat-PCAF interaction. Acetylation at Lys50 creates a new site for binding to PCAF and dictates the formation of a ternary complex of Tat-PCAF-P-TEFb. Thus, differential lysine acetylation of Tat coordinates the interactions with its co-activators, cyclin T1 and PCAF. Our results may help in understanding the ordered recruitment of Tat co-activators to the HIV-1 promoter.