Tat acetylation regulates its actions on microtubule dynamics and apoptosis in T lymphocytes
Tat acetylation regulates its actions on microtubule dynamics and apoptosis in T lymphocytes
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Tat 乙酰化调节其对 T 淋巴细胞微管动力学和凋亡的作用
DOI：
10.1002/path.2768
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发表时间：
2011-01-01
影响因子：
7.3
通讯作者：
Zhou, Jun
中科院分区：
文献类型：
--
作者：
Huo, Lihong;Li, Dengwen;Zhou, Jun
人类免疫缺陷病毒1型(HIV-1)的反式激活蛋白TAT被认为可以抑制微管动力学，从而触发T淋巴细胞的凋亡。TAT的这些作用构成了与获得性免疫缺陷综合征相关的T淋巴细胞大量破坏的主要机制之一。在这里，我们证明了赖氨酸-28(K28)上的TAT乙酰化增强了它与微管的相互作用，并通过降低微管蛋白聚合成微管的临界浓度来增加其促进微管组装的活性。此外，K28乙酰化增强了TAT稳定微管的能力，导致T淋巴细胞凋亡增加。我们的数据进一步表明，K28处的TAT乙酰化刺激其活性，诱导Bim从微管到线粒体的移位，Bim是Bcl-2家族的促凋亡蛋白。这些发现提供了第一个证据，表明TAT乙酰化除了调节其反式激活活性外，还调节其对微管动力学和细胞凋亡的作用。版权所有(C)2010年大不列颠和爱尔兰病理学会。作者：John Wiley&Sons，Ltd.
The transactivator protein Tat of human immunodeficiency virus type 1 (HIV-1) is known to suppress microtubule dynamics and thereby trigger apoptosis in T lymphocytes. These actions of Tat constitute one of the major mechanisms for the massive destruction of T lymphocytes associated with the acquired immunodeficiency syndrome. Herein, we show that Tat acetylation at lysine-28 (K28) enhances its interaction with microtubules and increases its activity to promote microtubule assembly, by lowering the critical concentration of tubulin for polymerization into microtubules. In addition, K28 acetylation enhances the ability of Tat to stabilize microtubules, leading to increased apoptosis in T lymphocytes. Our data further reveal that Tat acetylation at K28 stimulates its activity to induce the translocation of Bim, a pro-apoptotic protein of the Bcl-2 family, from microtubules to mitochondria. These findings provide the first evidence that Tat acetylation regulates its actions on microtubule dynamics and apoptosis, in addition to the regulation of its transactivation activity. Copyright (C) 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.