ArticleThe Journal of clinical investigation2024
The alanyl-tRNA synthetase AARS1 moonlights as a lactyltransferase to promote YAP signaling in gastric cancer.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 237 papers.
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Who cites it
237 citing papers in PubMed, 227 citations in OpenAlex.
- Lactylation in gastric cancer: From mechanisms to clinical applications (Review).Molecular medicine reports · 2026Review
- Lactate Signal: Modulator of Cellular Energy Production and Anabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Lysine pyruvylation: decoding the molecular language of pyruvate signaling.EMBO molecular medicine · 2026Article
- Lactylation-dependent DDX18 nucleolar escape regulates CD44 mRNA stability to drive fibrotic progression in kidney injury.The Journal of clinical investigation · 2026Article
- AARS2-SIRT5-Driven DLD K445 Lactylation Promotes Cuproptosis Resistance in Glioblastoma Stem Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A Metabolic-Epigenetic Axis of AARS1/IGF2BP3-K280 Lactylation Sustains Endometrial Cancer Stemness and Recurrence.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- 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
- Lactylation Remodels Tumorigenesis, Immune Microenvironment, and Therapeutic Response.Current issues in molecular biology · 2026Review
- Lactate as a metabolic-epigenetic hub in neurological disorders.Metabolic brain disease · 2026Review
- Research progress of lactylation modification in tumors (Review).Experimental and therapeutic medicine · 2026Review
- Lactylation Modification and Esophageal Cancer: Research Progress From Hypoxia-Induced Metabolic Reprogramming to Immune Escape.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- AARS1-Mediated H3K27 Lactylation Rewires Glycolysis to Sustain Aggressive and Recurrent Bladder Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Lactate metabolism and protein lactylation in inflammatory and tumor microenvironments.Molecular biomedicine · 2026Review
- Covalent allosteric inhibition of AARS1 lactyltransferase.Nature communications · 2026Article
- Targeting lactylation in hepatocellular carcinoma: Mechanistic insights and therapeutic opportunities (Review).International journal of molecular medicine · 2026Review
- Lysine l-Lactylation: Bridging Metabolism, Chromatin and Disease.Cell proliferation · 2026Review
- Unveiling Lactylation: A Novel Frontier in Cancer Stemness and Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- AARS1-catalyzed H4K12 lactylation promotes HCC resistance to targeted therapy by activating RAPGEF3-RAP1 signaling.Cell death & disease · 2026Article
- Global profiling of the protein lactylome in porcine liver.BMC genomics · 2026Article
177 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lactylation has been recently identified as a new type of posttranslational modification occurring widely on lysine residues of both histone and nonhistone proteins. The acetyltransferase p300 is thought to mediate protein lactylation, yet the cellular concentration of the proposed lactyl-donor, lactyl-coenzyme A, is about 1,000 times lower than that of acetyl-CoA, raising the question of whether p300 is a genuine lactyltransferase. Here, we report that alanyl-tRNA synthetase 1 (AARS1) moonlights as a bona fide lactyltransferase that directly uses lactate and ATP to catalyze protein lactylation. Among the candidate substrates, we focused on the Hippo pathway, which has a well-established role in tumorigenesis. Specifically, AARS1 was found to sense intracellular lactate and translocate into the nucleus to lactylate and activate the YAP-TEAD complex; and AARS1 itself was identified as a Hippo target gene that forms a positive-feedback loop with YAP-TEAD to promote gastric cancer (GC) cell proliferation. Consistently, the expression of AARS1 was found to be upregulated in GC, and elevated AARS1 expression was found to be associated with poor prognosis for patients with GC. Collectively, this work found AARS1 with lactyltransferase activity in vitro and in vivo and revealed how the metabolite lactate is translated into a signal of cell proliferation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.