Details

Autor(en) / Beteiligte

• Liu, Dongyang
• Xiao, Weidi
• Li, Haoting
• Zhang, Yanling
• Yuan, Shouli
• Li, Chengxi
• Dong, Suwei
• Wang, Chu

Titel

Discovery of Itaconate-Mediated Lysine Acylation

Ist Teil von

• Journal of the American Chemical Society, 2023-06, Vol.145 (23), p.12673-12681

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2023

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Itaconate is an important antimicrobial and immunoregulatory metabolite involved in host–pathogen interactions. A key mechanistic action of itaconate is through the covalent modification of cysteine residues via Michael addition, resulting in “itaconation”. However, it is unclear whether itaconate has other regulatory mechanisms. In this work, we discovered a novel type of post-translational modification by promiscuous antibody enrichment and data analysis with the open-search strategy and further confirmed it as the lysine “itaconylation”. We showed that itaconylation and its precursor metabolite itaconyl-CoA undergo significant upregulation upon lipopolysaccharides (LPS) stimulation in RAW264.7 macrophages. Quantitative proteomics identified itaconylation sites in multiple functional proteins, including glycolytic enzymes and histones, some of which were confirmed by synthetic peptide standards. The discovery of lysine itaconylation opens up new areas for studying how itaconate participates in immunoregulation via protein post-translational modification.