ArticleNature chemical biology2012
Trp-tRNA synthetase bridges DNA-PKcs to PARP-1 to link IFN-γ and p53 signaling.
Article in Nature chemical biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
61 citing papers in PubMed, 104 citations in OpenAlex.
- DNA-PKcs and PARP1 at the interface between DNA damage responses and cGAS-STING signaling: context-dependent roles and therapeutic implications.Cancer biology & therapy · 2026Review
- Nuclear localization of the glutaminyl-tRNA synthetase QARS reveals its role in DNA damage response in ovarian cancer.Nature communications · 2026Article
- Human aminoacyl-tRNA synthetases as integrators of translation and cell signalling networks.Nature reviews. Molecular cell biology · 2026Review
- PARP1 and PARP2 are dispensable for DNA repair by microhomology-mediated end-joining at double-ended DSBs.Nucleic acids research · 2026Article
- Aminoacyl-tRNA synthetases in tumor immunity: canonical translation, source-resolved immune circuits and therapeutic opportunities.Frontiers in immunology · 2026Review
- Programmed cell death in triple-negative breast cancer.Cellular & molecular biology letters · 2025Review
- Article
- Multifaceted impact of HIV inhibitor dapivirine on triple negative breast cancer cells reveals potential entities as targets for novel therapy.Scientific reports · 2024Article
- AKT-dependent nuclear localization of EPRS1 activates PARP1 in breast cancer cells.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The multifaceted functions of DNA-PKcs: implications for the therapy of human diseases.MedComm · 2024Review
- The high-affinity tryptophan uptake transport system in human cells.Biochemical Society transactions · 2024Review
- Article
- Tryptophanylation of insulin receptor by WARS attenuates insulin signaling.Cellular and molecular life sciences : CMLS · 2024Article
- Fushenmu treatment ameliorates RyR2 with related metabolites in a zebrafish model of barium chloride induced arrhythmia.Chinese medicine · 2023Article
- Nutrient sensors and their crosstalk.Experimental & molecular medicine · 2023Review
- Regulation of BRCA1 stability through the tandem UBX domains of isoleucyl-tRNA synthetase 1.Nature communications · 2022Article
- Functional and pathologic association of aminoacyl-tRNA synthetases with cancer.Experimental & molecular medicine · 2022Review
- DNA-PKcs: A Targetable Protumorigenic Protein Kinase.Cancer research · 2022Review
- tRNA biogenesis and specific aminoacyl-tRNA synthetases regulate senescence stability under the control of mTOR.PLoS genetics · 2021Article
- The regulatory roles of aminoacyl-tRNA synthetase in cardiovascular disease.Molecular therapy. Nucleic acids · 2021Review
1 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Interferon-γ (IFN-γ) engenders strong antiproliferative responses, in part through activation of p53. However, the long-known IFN-γ-dependent upregulation of human Trp-tRNA synthetase (TrpRS), a cytoplasmic enzyme that activates tryptophan to form Trp-AMP in the first step of protein synthesis, is unexplained. Here we report a nuclear complex of TrpRS with the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) and with poly(ADP-ribose) polymerase 1 (PARP-1), the major PARP in human cells. The IFN-γ-dependent poly(ADP-ribosyl)ation of DNA-PKcs (which activates its kinase function) and concomitant activation of the tumor suppressor p53 were specifically prevented by Trp-SA, an analog of Trp-AMP that disrupted the TrpRS-DNA-PKcs-PARP-1 complex. The connection of TrpRS to p53 signaling in vivo was confirmed in a vertebrate system. These and further results suggest an unexpected evolutionary expansion of the protein synthesis apparatus to a nuclear role that links major signaling pathways.
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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.