ArticleNature communications2024
Targeted degradation of extracellular mitochondrial aspartyl-tRNA synthetase modulates immune responses.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- DARS2 Promotes Tumorigenesis and Metastasis by Activating PI3K/Akt/GSK-3β/β-Catenin Signaling Pathway in Breast Cancer.The Kaohsiung journal of medical sciences · 2026Article
- The deubiquitinase USP4 stabilizes the SCFNature communications · 2026Article
- DARS2 serves as an independent prognostic factor and participates in multiple biological processes in bladder urothelial carcinoma.Translational andrology and urology · 2026Article
- AAV9-DARS2 Gene Therapy Rescues Phenotype in Leukoencephalopathy with Brainstem and Spinal Cord Involvement and Lactate Elevation Patient Cells and Neuronal Dars2 Deficient Mice.Annals of neurology · 2026Article
- Ubiquitin E3 ligase MARCH10 targets influenza hemagglutinin for ubiquitination.Cellular signalling · 2025Article
- Secreted mitochondrial aspartyl-tRNA synthetase (DARS2) regulates TNFα signaling.Physiological reports · 2025Article
- NSP7 Molecular Degrader Attenuates Coronaviral Infection Through the β-TrCP1/FBXO5 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Reciprocal Regulation Between the SCFbioRxiv : the preprint server for biology · 2025Article
- Decoding tRNA dynamics in neuroimmune disorders: mechanistic insights, diagnostic innovations, and therapeutic opportunities.Frontiers in immunology · 2025Review
- FOXK2 targeting by the SCF-E3 ligase subunit FBXO24 for ubiquitin mediated degradation modulates mitochondrial respiration.The Journal of biological chemistry · 2024Article
Corrections and comments
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Authors and funding
22 authors.
Funding
Abstract
The severity of bacterial pneumonia can be worsened by impaired innate immunity resulting in ineffective pathogen clearance. We describe a mitochondrial protein, aspartyl-tRNA synthetase (DARS2), which is released in circulation during bacterial pneumonia in humans and displays intrinsic innate immune properties and cellular repair properties. DARS2 interacts with a bacterial-induced ubiquitin E3 ligase subunit, FBXO24, which targets the synthetase for ubiquitylation and degradation, a process that is inhibited by DARS2 acetylation. During experimental pneumonia, Fbxo24 knockout mice exhibit elevated DARS2 levels with an increase in pulmonary cellular and cytokine levels. In silico modeling identified an FBXO24 inhibitory compound with immunostimulatory properties which extended DARS2 lifespan in cells. Here, we show a unique biological role for an extracellular, mitochondrially derived enzyme and its molecular control by the ubiquitin apparatus, which may serve as a mechanistic platform to enhance protective host immunity through small molecule discovery.
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Registered trials
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.