PRMT1-Mediated LDHA Methylation Drives STAT3 Lactylation to Orchestrate Intestinal Inflammation and Tumorigenesis - PubMed
4 hours ago
- #immunometabolism
- #inflammatory bowel disease
- #post-translational modification
- The study identifies a methionine-SAM-PRMT1-LDHA-lactate metabolic axis in macrophages that regulates intestinal inflammation via STAT3.
- PRMT1 methylates LDHA at R268/R269, increasing LDHA activity and lactate production, which drives STAT3 lactylation at K709.
- STAT3 lactylation stabilizes an open conformation, facilitating Y705 phosphorylation and anti-inflammatory IL-10 expression in macrophages.
- Genetic deletion of PRMT1 in myeloid cells impairs STAT3 activation, exacerbating colitis and promoting inflammation-associated tumorigenesis.
- Inhibition of STAT3 K709 lactylation blocks STAT3 activation and worsens colitis, highlighting lactylation as a key metabolic regulator.