Substrate and Functional Diversity of Lysine Acetylation Revealed by a Proteomics Survey

Sung Chan Kim, Robert Sprung, Yue Chen, Yingda Xu, Haydn Ball, Jimin Pei, Tzuling Cheng, Yoonjung Kho, Hao Xiao, Lin Xiao, Nick V. Grishin, Michael White, Xiang Jiao Yang, Yingming Zhao

Research output: Contribution to journalArticlepeer-review

1286 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)607-618
Number of pages12
JournalMolecular Cell
Issue number4
StatePublished - Aug 18 2006

Bibliographical note

Funding Information:
This work was supported by The Robert A. Welch Foundation (I-1550 to Y.Z. and I-1414 to M.W.), NCI/NIH's “Innovative Technologies for the Molecular Analysis of Cancer” program (CA107943 to Y.Z.), the National Cancer Institute of Canada (to X.-J.Y.), and the Canadian Institutes for Health Research (to X.-J.Y.). We thank Steve McKnight and Shanhai Xie for preparation of liver mitochondria and Hui Zhou for the density map analysis. We are grateful to Wei Gu, Jun Qin, and Helen Yin for their insightful suggestions. We also thank John Cottrell from MatrixScience for his assistance.




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