Di Zhang, Jinjun Gao, Zhijun Zhu, Qianying Mao, Zhiqiang Xu, Pankaj K. Singh, Cornelius C. Rimayi, Carlos Moreno-Yruela, Shuling Xu, Gongyu Li, Yi-Cheng Sin, Yue Chen, Christian A. Olsen, Nathaniel W. Snyder, Lunzhi Dai, Lingjun Li, Yingming Zhao
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引用次数: 0
Abstract
Lysine l-lactylation (Kl-la) is a novel protein posttranslational modification (PTM) driven by l-lactate. This PTM has three isomers: Kl-la, N-ε-(carboxyethyl)-lysine (Kce) and d-lactyl-lysine (Kd-la), which are often confused in the context of the Warburg effect and nuclear presence. Here we introduce two methods to differentiate these isomers: a chemical derivatization and high-performance liquid chromatography analysis for efficient separation, and isomer-specific antibodies for high-selectivity identification. We demonstrated that Kl-la is the primary lactylation isomer on histones and dynamically regulated by glycolysis, not Kd-la or Kce, which are observed when the glyoxalase system was incomplete. The study also reveals that lactyl-coenzyme A, a precursor in l-lactylation, correlates positively with Kl-la levels. This work not only provides a methodology for distinguishing other PTM isomers, but also highlights Kl-la as the primary responder to glycolysis and the Warburg effect.
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