Substrate and functional diversity of lysine acetylation revealed by a proteomics survey.
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.
Kim
Sung Chan
SC
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Sprung
Robert
R
Chen
Yue
Y
Xu
Yingda
Y
Ball
Haydn
H
Pei
Jimin
J
Cheng
Tzuling
T
Kho
Yoonjung
Y
Xiao
Hao
H
Xiao
Lin
L
Grishin
Nick V
NV
White
Michael
M
Yang
Xiang-Jiao
XJ
Zhao
Yingming
Y
D000107:Acetylation; D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D019295:Computational Biology; D005347:Fibroblasts / Q000166:cytology; D006367:HeLa Cells; D006801:Humans; D008239:Lysine / Q000737:chemistry / Q000378:metabolism*; D013058:Mass Spectrometry; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D010455:Peptides / Q000737:chemistry; D011506:Proteins / Q000737:chemistry / Q000302:isolation & purification; D040901:Proteomics; D013379:Substrate Specificity
D010455:Peptides; D011506:Proteins; D008239:Lysine