Product Overview
Lactylation proteomics is a novel post-translational modification proteomics technique that qualitatively or quantitatively evaluates the lactation modification sites, types, and levels of proteomes at the omics level. First reported in *Nature* in 2019, this modification reveals that lactate can covalently modify histone lysine sites as a metabolic signaling molecule, and is widely involved in the pathological regulation of diseases such as tumors, immune disorders, cardiovascular diseases, and neurological diseases, making it a hot research topic both domestically and internationally.
Wininnovate Bio’s quantitative lactation modification omics analysis project is based on the high-speed, high-resolution, high dynamic range timsTOF HT mass spectrometer and uses IP-4D-DIA technology. Through specific antibody enrichment and high-depth mass spectrometry detection, it can identify the lactation modification status in samples at a high throughput at the macro-omics level, and rapidly expand the breadth and depth of related research.
Technical Process
Lactic acidification enrichment principle: Magnetic beads are coupled with a specific pan-lactation antibody (Pan-Kla) to selectively capture modified peptides containing lactated lysine in a mixture of enzymatically hydrolyzed peptides through an immunoaffinity reaction.
Schematic diagram of lactation modification omics process route
Applications
English Title：NBS1 lactylation is required for efficient DNA repair and chemotherapy resistance
Impact Factor：50.5
Journal：Nature
Research Content：This study reveals that lactation modification is a key mechanism driving chemotherapy resistance in tumors: In the chemotherapeutic DNA damage microenvironment, enhanced glycolysis in tumor cells leads to lactate accumulation. Lactic acid remodels chromatin accessibility through histone H3K18 lactation modification, promoting lactation at the K388 site of NBS1, the core subunit of the MRE11-RAD50-NBS1 (MRN) complex. This modification is mediated by the acetyltransferase TIP60, enabling NBS1 and MRE11 to efficiently assemble into an active MRN complex, initiating the homologous recombination repair (HRR) pathway, maintaining genomic stability, and conferring chemotherapy resistance to tumor cells. Targeted inhibition of lactation modification can significantly enhance the efficacy of chemotherapy. Through quantitative lactation modification proteomics analysis, the study systematically identified the key modification site of NBS1 K388 lactation in chemotherapy-resistant tumor cells. Verification using site-specific antibodies and gene-edited mutants confirmed that this modification is a molecular switch regulating the assembly of the MRN complex and the efficiency of DNA repair.
English Title：Alanyl-tRNA synthetase, AARS1, is a lactate sensor and lactyltransferase that lactylates p53 and contributes to tumorigenesis
Impact Factor：45.5
Journal：cELL
Research Content：This study is the first to identify alanine-tRNA synthetase AARS1 as an intracellular lactate sensor and lactate transferase, revealing a novel mechanism by which the metabolite lactate regulates tumorigenesis through non-histone lactation modification. The study found that AARS1 can directly bind lactate and transfer it to the DNA-binding domain (DBD) of the p53 protein, catalyzing lactation modification at p53 K120 and K139 sites. This leads to conformational changes in p53 and inhibition of liquid-liquid phase separation (LLPS), thereby suppressing p53's transcriptional activation function and tumor suppressor activity, ultimately promoting tumorigenesis. This study systematically identified the AARS1-mediated p53 lactation site through quantitative lactation modification proteomics analysis, confirming that this modification is a key molecular switch connecting the Warburg effect and tumor suppression, providing a theoretical basis for developing new tumor treatment strategies targeting the lactate metabolism pathway. This discovery, together with the concurrently published Nature study "AARS1/AARS2 as Global Lysine Lactate Transferases Regulating cGAS," establishes the core position of the AARS family proteins as "writers" of lactation modifications, marking a milestone breakthrough in lactation research in 2024.
Sample Submission Requirements
- Sample
- Routine Animal Tissues (brain, liver, spleen, lung, kidney, muscle, etc.)
- Specification
- 300mg-1g
- Notes
- Sample
- Plant Tissues (leaves, flowers, etc.)
- Specification
- 5-10g
- Notes
- For high-moisture/high-polysaccharide tissues (such as fruits, tubers, and mature leaves), the sample size should be 10-15g.
- Sample
- cell
- Specification
- 10^8
- Notes
| Sample | Specification | Notes |
|---|---|---|
| Routine Animal Tissues (brain, liver, spleen, lung, kidney, muscle, etc.) | 300mg-1g | |
| Plant Tissues (leaves, flowers, etc.) | 5-10g | For high-moisture/high-polysaccharide tissues (such as fruits, tubers, and mature leaves), the sample size should be 10-15g. |
| cell | 10^8 |
References
Chen H, Li Y, Li H, Chen X, Fu H, Mao D, Chen W, Lan L, Wang C, Hu K, Li J, Zhu C, Evans I, Cheung E, Lu D, He Y, Behrens A, Yin D, Zhang C NBS1 lactylation is required for efficient DNA repair and chemotherapy resistance Nature, 2024 Jul;631(8021):663-669.DOI: 10.1038/s41586-024-07620-9. Epub 2024 Jul 3. PMID: 38961290; PMCID: PMC11254748
Zong Z, Xie F, Wang S, Wu X, Zhang Z, Yang B, Zhou F Alanyl-tRNA synthetase, AARS1, is a lactate sensor and lactyltransferase that lactylates p53 and contributes to tumorigenesis Cell, 2024 May;187(10):2375-2392.e33.DOI: 10.1016/j.cell.2024.04.002. Epub 2024 Apr 22. PMID: 38653238
Chen Y, Wu J, Zhai L, Zhang T, Yin H, Gao H, Zhao F, Wang Z, Yang X, Jin M, Huang B, Ding X, Li R, Yang J, He Y, Wang Q, Wang W, Kloeber JA, Li Y, Hao B, Zhang Y, Wang J, Tan M, Li K, Wang P, Lou Z, Yuan J Metabolic regulation of homologous recombination repair by MRE11 lactylation Cell, 2024 Jan;18;187(2):294-311.e21.DOI: 10.1016/j.cell.2023.11.022. Epub 2023 Dec 20. PMID: 38128537; PMCID: PMC11725302
Shenzhen Wininnovate Bio Co., Ltd.
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