Substrate and functional diversity of lysine acetylation revealed by a proteomics survey
Substrate and functional diversity of lysine acetylation revealed by a proteomics survey
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DOI：
10.1016/j.molcel.2006.06.026
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发表时间：
2006-08-18
期刊：
影响因子：
16
通讯作者：
Zhao, Yingming
中科院分区：
文献类型：
--
作者：
Kim, Sung Chan;Sprung, Robert;Zhao, Yingming
赖氨酸残基上的蛋白质乙酰化是一种动态的翻译后修饰，已知其在调节转录和其他DNA依赖性核过程中起关键作用。然而，这种修饰在不同细胞蛋白中的程度在很大程度上仍然未知，这是赖氨酸乙酰化生物学的主要瓶颈。在这里，我们报告的第一个蛋白质组学调查的修改，确定388乙酰化位点的195个蛋白质之间的蛋白质来源于HeLa细胞和小鼠肝线粒体。除了基于染色质的细胞过程的调节剂，具有不同功能的非核定位蛋白被确定。最引人注目的是，超过20%的线粒体蛋白质中发现了乙酰赖氨酸，包括许多长寿调节因子和代谢酶。我们的研究揭示了赖氨酸乙酰化在调节细胞核外多种细胞通路中以前未被重视的作用。合并后的数据集为进一步表征这种修饰对细胞生理学和人类疾病的贡献提供了丰富的来源。
Acetylation of proteins on lysine residues is a dynamic posttranslational modification that is known to play a key role in regulating transcription and other DNA-dependent nuclear processes. However, the extent of this modification in diverse cellular proteins remains largely unknown, presenting a major bottleneck for lysine-acetylation biology. Here we report the first proteomic survey of this modification, identifying 388 acetylation sites in 195 proteins among proteins derived from HeLa cells and mouse liver mitochondria. In addition to regulators of chromatin-based cellular processes, nonnuclear localized proteins with diverse functions were identified. Most strikingly, acetyllysine was found in more than 20% of mitochondrial proteins, including many longevity regulators and metabolism enzymes. Our study reveals previously unappreciated roles for lysine acetylation in the regulation of diverse cellular pathways outside of the nucleus. The combined data sets offer a rich source for further characterization of the contribution of this modification to cellular physiology and human diseases.