Trp-tRNA synthetase bridges DNA-PKcs to PARP-1 to link IFN-γ and p53 signaling
العنوان: | Trp-tRNA synthetase bridges DNA-PKcs to PARP-1 to link IFN-γ and p53 signaling |
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المؤلفون: | Mili Kapoor, Paul Schimmel, Quansheng Zhou, Shuji Kishi, Sunhee Lee, Mathew Sajish, Xiang-Lei Yang, Delgado M. Valdez, Min Guo, Sunghoon Kim |
المصدر: | Nature chemical biology. 8(6) |
سنة النشر: | 2011 |
مصطلحات موضوعية: | Models, Molecular, Cytoplasm, Embryo, Nonmammalian, Immunoprecipitation, Protein subunit, Poly ADP ribose polymerase, Cell Culture Techniques, Poly (ADP-Ribose) Polymerase-1, Tryptophan-tRNA Ligase, DNA-Activated Protein Kinase, Biology, Transfection, Article, Interferon-gamma, Catalytic Domain, Animals, Humans, Protein Interaction Maps, Phosphorylation, Protein kinase A, Molecular Biology, DNA-PKcs, Zebrafish, Cell Nucleus, Microscopy, Confocal, Kinase, Cell Biology, Molecular biology, Electrophoresis, Polyacrylamide Gel, Signal transduction, Poly(ADP-ribose) Polymerases, Tumor Suppressor Protein p53, HeLa Cells, Signal Transduction |
الوصف: | 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. |
تدمد: | 1552-4469 |
الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5388b55ab67f14644ccf7ecd2a7881a8Test https://pubmed.ncbi.nlm.nih.gov/22504299Test |
حقوق: | OPEN |
رقم الانضمام: | edsair.doi.dedup.....5388b55ab67f14644ccf7ecd2a7881a8 |
قاعدة البيانات: | OpenAIRE |