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Updated: Jun 23, 2026
07:26
Site Specific Lysine Acetylation of Histones for Nucleosome Reconstitution using Genetic Code Expansion in Escherichia coli
Published on: December 26, 2020
Lactylation: a novel post-translational modification for cGAS-STING pathway
Hongquan Wang1,2,3, Zhiji Wang4, Fanyu Meng5
1Department of Geriatrics, Aerospace Center Hospital, Peking University Aerospace School of Clinical Medicine, Beijing, 100049, China.
Summary
Lysine lactylation (Kla) regulates the cGAS-STING pathway, impacting innate immunity in various diseases. Targeting this metabolic-epigenetic modification offers novel therapeutic strategies for autoimmune disorders, cancer, and neuroinflammation.
Area of Science:
- Immunometabolism
- Epigenetics
- Post-translational modifications
Background:
- Lysine lactylation (Kla) is a metabolic-epigenetic regulator linking cellular metabolism to innate immune signaling.
- The cGAS-STING pathway is crucial for innate immunity and is influenced by metabolic states.
- The specific role of lactylation in modulating the cGAS-STING pathway requires synthesis.
Purpose of the Study:
- To analyze the molecular mechanisms of lysine lactylation in regulating the cGAS-STING signaling axis.
- To discuss the pathophysiological implications of lactylation in diseases.
- To explore the therapeutic potential of targeting lactylation in autoimmunity, neuroinflammation, and cancer.
Main Methods:
- Comprehensive literature review.
- Summarized the biochemical basis of lactylation (writers, erasers, readers).
- Examined evidence of direct and indirect regulation of cGAS-STING by lactylation, including disease models and therapeutic interventions.
Main Results:
- Lactylation directly modifies cGAS and STING, affecting their stability, activity, and signaling.
- Lactylation has dual effects: enhancing interferon responses in autoimmune diseases and hypoxic-ischemic encephalopathy, but suppressing cGAS-STING in cancer and neuropathic pain.
- Indirect regulation involves lactylation's influence on cytosolic DNA availability and repair, with identified lactyltransferases and delactylases.
Conclusions:
- Lactylation acts as a metabolic-immune checkpoint, fine-tuning cGAS-STING signaling in a disease-specific manner.
- Targeting the lactylation axis presents a novel immunometabolic therapeutic strategy.
- Potential applications include treating autoimmune disorders, chronic infections, neurodegeneration, and cancer.
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