Tip60 acetyltransferase activity is controlled by phosphorylation
Tip60 acetyltransferase activity is controlled by phosphorylation
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DOI：
10.1074/jbc.m211811200
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发表时间：
2003-02-14
影响因子：
4.8
通讯作者：
Khochbin, S
中科院分区：
文献类型：
--
作者：
Lemercier, C;Legube, G;Khochbin, S
在这里，我们表明，磷酸化组蛋白乙酰转移酶Tip 60，目标的人类免疫缺陷病毒，1型编码的反式激活因子达特，在控制其催化活性中起着至关重要的作用。基于杆状病毒的表达和纯化Tip 60结合质谱法允许鉴定丝氨酸86和90作为体内磷酸化的两个主要位点。发现Tip 60的磷酸化调节其组蛋白乙酰转移酶活性。其中一个磷酸化丝氨酸Ser-90位于细胞周期蛋白B/Cdc 2的共有位点。Ser-90在体外被cyclin B/Cdc 2复合物特异性磷酸化。因此，在药物诱导的G（2）/M期细胞停滞后，Tip 60的磷酸化增强。用细胞周期蛋白依赖性激酶的特异性抑制剂roscovitin处理细胞，可以消除Tip 60的G（2）/M依赖性磷酸化。总的来说，这些结果强烈地表明Tip 60活性的G（2）/M依赖性控制。
Here we show that the phosphorylation of histone acetyltransferase Tip60, a target of human immunodeficiency virus, type 1-encoded transactivator Tat, plays a crucial role in the control of its catalytic activity. Baculovirus-based expression and purification of Tip60 combined with mass spectrometry allowed the identification of serines 86 and 90 as two major sites of phosphorylation in vivo. The phosphorylation of Tip60 was found to modulate its histone acetyltransferase activity. One of the identified phosphorylated serines, Ser-90, was within a consensus cyclin B/Cdc2 site. Ser-90 was specifically phosphorylated in vitro by the cyclin B/Cdc2 complex. Accordingly, the phosphorylation of Tip60 was enhanced after drug-induced arrest of cells in G(2)/M. This G(2)/M-dependent phosphorylation of Tip60 was abolished by treating cells with a specific inhibitor of the cyclin-dependent kinase, roscovitin. All together, these results strongly suggest a G(2)/M-dependent control of Tip60 activity.