ArticleNature communications2025
Genetic code expansion reveals site-specific lactylation in living cells reshapes protein functions.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed.
- Lactylation in gastric cancer: From mechanisms to clinical applications (Review).Molecular medicine reports · 2026Review
- Lactate-Mediated Lysine Lactylation in Renal Fibrosis: Current Progress and Challenges.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- Lactate metabolism and protein lactylation in inflammatory and tumor microenvironments.Molecular biomedicine · 2026Review
- Novel protein acylations in Alzheimer's disease: Molecular, mechanisms, biological significance, and diagnostic and therapeutic potentials.Journal of advanced research · 2026Review
- Protein lactylation in health and diseases: molecular mechanisms, biological significance, and clinical implications.Signal transduction and targeted therapy · 2026Review
- HDAC3 as an Immunometabolic Rheostat: Molecular Mechanisms of Deacylation Plasticity, Lactylation Dynamics, and Spatiotemporal Regulation.Biomolecules · 2026Review
- Training PBertKla on an Integrated Multi-Source Dataset with a Machine-Learning Layer for Lysine Lactylation Site Prediction.International journal of molecular sciences · 2026Article
- DHX9 transcriptional upregulation and lactylation at K1024 fuels a glycolysis-histone lactylation loop in osteosarcoma.Journal of translational medicine · 2026Article
- PKM2 Lactylation Promotes Colorectal Cancer Vasculogenic Mimicry and Bevacizumab Resistance by Facilitating FOSL1 Super-enhancer Formation.Cancer research · 2026Article
- Lactylation-regulated ferroptosis: mechanisms, disease associations, and therapeutic strategies.Archives of pharmacal research · 2026Review
- Development and validation of an interpretable prognostic model for bladder cancer based on lactylation associated genes using SHAP analysis.Discover oncology · 2026Article
- Site-Specific incorporation of lysine acetyl-methylation into proteins.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Article
- Protein lactylation: a metabolic signal driving cancer therapy resistance.Cell death discovery · 2026Review
- Lactylation and acetylation: parallel paths, divergent deeds, and research dilemmas.Journal of translational medicine · 2026Review
- PDK4-driven lactate accumulation facilitates LPCAT2 lactylation to exacerbate sepsis-induced acute lung injury.Cell death and differentiation · 2026Article
- Glycolysis enzymes and cellular lactylation in tumour.Clinical and translational medicine · 2026Review
- HSPA8 lactylation attenuates neuronal pyroptosis via E3 ligase-mediated NLRP3 degradation after ischemic stroke.Apoptosis : an international journal on programmed cell death · 2026Article
- Metabolism-driven emerging acylation modifications in COPD: from elucidation of fundamental mechanisms to clinical diagnosis and treatment.Frontiers in immunology · 2026Review
- Role of lactylation modification in regulating lytic cell death.Frontiers in oncology · 2026Review
- Lactylation in urological malignancies: emerging mechanisms and therapeutic direction.Frontiers in cell and developmental biology · 2026Review
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
Protein lactylation is an emerging field. To advance the exploration of its biological functions, here we develop a comprehensive workflow that integrates proteomics to identify lactylated sites, genetic code expansion (GCE) for the expression of site-specifically lactylated proteins in living cells, and an integrated functional analysis (IFA) platform to evaluate their biological effects. Using a combined wet-and-dry-lab proteomics strategy, we identify a conserved lactylation at ALDOA-K147, which we hypothesize plays a significant biological role. Expression of this site-specifically lactylated ALDOA in mammalian cells reveals that this modification not only inhibits enzymatic activity but also induces gain-of-function effects. These effects reshaped ALDOA functionality by enhancing protein stability, promoting nuclear translocation, regulating adhesion-related gene expression, altering cell morphology and modulating ALDOA-interacting proteins. Our findings highlight the utility of the GCE-based workflow in establishing causal relationships between specific lactylation events and both target-specific and cell-wide changes, advancing our understanding of protein lactylation's functional impact.
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