Tubulin acetylation favors Hsp90 recruitment to microtubules and stimulates the signaling function of the Hsp90 clients Akt/PKB and p53
Tubulin acetylation favors Hsp90 recruitment to microtubules and stimulates the signaling function of the Hsp90 clients Akt/PKB and p53
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DOI：
10.1016/j.cellsig.2008.12.004
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发表时间：
2009-04-01
影响因子：
4.8
通讯作者：
Baillet, Anita
中科院分区：
文献类型：
--
作者：
Giustiniani, Julien;Daire, Vanessa;Baillet, Anita
微管是一种高度动态的聚合物，参与多种细胞过程，如信号转导，积累各种翻译后修饰，包括多聚谷氨酰化、多聚甘氨酰化、羧基末端切割和乙酰化，其功能才开始被揭示。分子伴侣热休克蛋白90，这是必不可少的折叠和活动的许多客户端蛋白参与细胞增殖和凋亡，与微管网络，但微管蛋白的翻译后修饰的影响，其微管结合尚未调查。在此，我们表明，组成型（β）和诱导型（α）Hsp 90亚型结合微管的方式，取决于微管蛋白乙酰化的水平。微管蛋白乙酰化还刺激至少两种其客户蛋白激酶Akt/PKB和转录因子p53的结合和信号传导功能。这项研究强调了微管蛋白乙酰化在调节微管为基础的运输热休克蛋白90伴侣蛋白，从而在调节细胞质中的信号动力学的作用。(C)2008年爱思唯尔公司All rights reserved.
Involved in a wide range of cellular processes such as signal transduction, microtubules are highly dynamic polymers that accumulate various post-translational modifications including polyglutamylation, polyglycylation, carboxyterminal cleavage and acetylation, the functions of which just begin to be uncovered. The molecular chaperone Hsp90, which is essential for the folding and activity of numerous client proteins involved in cell proliferation and apoptosis, associates with the microtubule network but the effects of tubulin post-translational modifications on its microtubule binding has not yet been investigated. Herein, we show that both the constitutive (beta) and the inducible (alpha) Hsp90 isoforms bind to microtubules in a way that depends on the level of tubulin acetylation. Tubulin acetylation also stimulates the binding and the signaling function of at least two of its client proteins, the kinase Akt/PKB and the transcription factor p53. This study highlights the role of tubulin acetylation in modulating microtubule-based transport of Hsp90-chaperoned proteins and thus in regulating signaling dynamics in the cytoplasm. (C) 2008 Elsevier Inc. All rights reserved.