TY - JOUR
T1 - The first identification of lysine malonylation substrates and its regulatory enzyme.
AU - Peng, Chao
AU - Lu, Zhike
AU - Xie, Zhongyu
AU - Cheng, Zhongyi
AU - Chen, Yue
AU - Tan, Minjia
AU - Luo, Hao
AU - Zhang, Y.
AU - He, Wendy
AU - Yang, K.
AU - Zwaans, Bernadette M M
AU - Tishkoff, Daniel
AU - Ho, Linh
AU - Lombard, David
AU - He, Tong Chuan
AU - Dai, Junbiao
AU - Verdin, Eric
AU - Ye, Yang
AU - Zhao, Yingming
PY - 2011/12
Y1 - 2011/12
N2 - Protein post-translational modifications (PTMs) at the lysine residue, such as lysine methylation, acetylation, and ubiquitination, are diverse, abundant, and dynamic. They play a key role in the regulation of diverse cellular physiology. Here we report discovery of a new type of lysine PTM, lysine malonylation (Kmal). Kmal was initially detected by mass spectrometry and protein sequence-database searching. The modification was comprehensively validated by Western blot, tandem MS, and high-performance liquid chromatography of synthetic peptides, isotopic labeling, and identification of multiple Kmal substrate proteins. Kmal is a dynamic and evolutionarily conserved PTM observed in mammalian cells and bacterial cells. In addition, we demonstrate that Sirt5, a member of the class III lysine deacetylases, can catalyze lysine demalonylation and lysine desuccinylation reactions both in vitro and in vivo. This result suggests the possibility of nondeacetylation activity of other class III lysine deacetylases, especially those without obvious acetylation protein substrates. Our results therefore reveal a new type of PTM pathway and identify the first enzyme that can regulate lysine malonylation and lysine succinylation status.
AB - Protein post-translational modifications (PTMs) at the lysine residue, such as lysine methylation, acetylation, and ubiquitination, are diverse, abundant, and dynamic. They play a key role in the regulation of diverse cellular physiology. Here we report discovery of a new type of lysine PTM, lysine malonylation (Kmal). Kmal was initially detected by mass spectrometry and protein sequence-database searching. The modification was comprehensively validated by Western blot, tandem MS, and high-performance liquid chromatography of synthetic peptides, isotopic labeling, and identification of multiple Kmal substrate proteins. Kmal is a dynamic and evolutionarily conserved PTM observed in mammalian cells and bacterial cells. In addition, we demonstrate that Sirt5, a member of the class III lysine deacetylases, can catalyze lysine demalonylation and lysine desuccinylation reactions both in vitro and in vivo. This result suggests the possibility of nondeacetylation activity of other class III lysine deacetylases, especially those without obvious acetylation protein substrates. Our results therefore reveal a new type of PTM pathway and identify the first enzyme that can regulate lysine malonylation and lysine succinylation status.
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U2 - 10.1074/mcp.M111.012658
DO - 10.1074/mcp.M111.012658
M3 - Article
C2 - 21908771
AN - SCOPUS:83055173304
SN - 1535-9484
VL - 10
JO - Molecular & cellular proteomics : MCP
JF - Molecular & cellular proteomics : MCP
IS - 12
ER -