Lysine Acetylation Targets Protein Complexes and Co-Regulates Major Cellular Functions
Lysine Acetylation Targets Protein Complexes and Co-Regulates Major Cellular Functions
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DOI：
10.1126/science.1175371
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发表时间：
2009-08-14
期刊：
影响因子：
56.9
通讯作者：
Mann, Matthias
中科院分区：
文献类型：
--
作者：
Choudhary, Chunaram;Kumar, Chanchal;Mann, Matthias
赖氨酸乙酰化是一种可逆的蛋白质翻译后修饰，在基因表达调控中起着关键作用。到目前为止，技术上的限制阻碍了对赖氨酸乙酰化的细胞作用的全面分析。我们使用高分辨率质谱鉴定了1750种蛋白质上的3600个赖氨酸乙酰化位点，并对脱乙酰酶抑制剂辛二酰苯胺异羟肟酸和MS-275的乙酰化变化进行了定量。赖氨酸乙酰化优先靶向参与不同细胞过程的大分子复合物，如染色质重塑、细胞周期、剪接、核转运和肌动蛋白成核。乙酰化损害磷酸化依赖的相互作用的14-3-3和调节酵母细胞周期蛋白依赖性激酶Cdc 28。我们的数据表明，赖氨酸乙酰化的监管范围是广泛的，并与其他主要的翻译后修饰。
Lysine acetylation is a reversible posttranslational modification of proteins and plays a key role in regulating gene expression. Technological limitations have so far prevented a global analysis of lysine acetylation's cellular roles. We used high-resolution mass spectrometry to identify 3600 lysine acetylation sites on 1750 proteins and quantified acetylation changes in response to the deacetylase inhibitors suberoylanilide hydroxamic acid and MS-275. Lysine acetylation preferentially targets large macromolecular complexes involved in diverse cellular processes, such as chromatin remodeling, cell cycle, splicing, nuclear transport, and actin nucleation. Acetylation impaired phosphorylation-dependent interactions of 14-3-3 and regulated the yeast cyclin-dependent kinase Cdc28. Our data demonstrate that the regulatory scope of lysine acetylation is broad and comparable with that of other major posttranslational modifications.