Academic Journal
OAS1/RNase L executes RIG-I ligand-dependent tumor cell apoptosis.
| العنوان: | OAS1/RNase L executes RIG-I ligand-dependent tumor cell apoptosis. |
|---|---|
| المؤلفون: | Boehmer, Daniel F R, Formisano, Simone, Hopfner, Karl-Peter, Endres, Stefan, Rothenfusser, Simon, Friedel, Caroline C, Duewell, Peter, Schnurr, Max, Koenig, Lars M, de Oliveira Mann, Carina C, Müller, Stephan A, Kluge, Michael, Metzger, Philipp, Rohlfs, Meino, Hörth, Christine, Kocheise, Lorenz, Lichtenthaler, Stefan |
| المصدر: | Science immunology 6(61), eabe2550 (2021). doi:10.1126/sciimmunol.abe2550 |
| بيانات النشر: | AAAS |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | info:eu-repo/classification/ddc/610, 2',5'-Oligoadenylate Synthetase: genetics, 2',5'-Oligoadenylate Synthetase: immunology, Adaptor Proteins, Signal Transducing: genetics, Animals, Apoptosis, Cell Line, Tumor, Coculture Techniques, DEAD Box Protein 58: genetics, Endoribonucleases: genetics, Endoribonucleases: immunology, Humans, Interferon-Induced Helicase, IFIH1: genetics, Ligands, Mice, Neoplasms: immunology, Receptors, Immunologic: genetics, Retinoic Acid: immunology |
| جغرافية الموضوع: | DE |
| الوصف: | Cytoplasmic double-stranded RNA is sensed by RIG-I-like receptors (RLRs), leading to induction of type I interferons (IFN-Is), proinflammatory cytokines, and apoptosis. Here, we elucidate signaling mechanisms that lead to cytokine secretion and cell death induction upon stimulation with the bona fide RIG-I ligand 5'-triphosphate RNA (3p-RNA) in tumor cells. We show that both outcomes are mediated by dsRNA-receptor families with RLR being essential for cytokine production and IFN-I-mediated priming of effector pathways but not for apoptosis. Affinity purification followed by mass spectrometry and subsequent functional analysis revealed that 3p-RNA bound and activated oligoadenylate synthetase 1 and RNase L. RNase L-deficient cells were profoundly impaired in their ability to undergo apoptosis. Mechanistically, the concerted action of translational arrest triggered by RNase L and up-regulation of NOXA was needed to deplete the antiapoptotic MCL-1 to cause intrinsic apoptosis. Thus, 3p-RNA-induced apoptosis is a two-step process consisting of RIG-I-dependent priming and an RNase L-dependent effector phase. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/pmid:34272227; info:eu-repo/semantics/altIdentifier/issn/2470-9468; https://pub.dzne.de/record/162740; https://pub.dzne.de/search?p=id:%22DZNE-2021-01397%22 |
| الاتاحة: | https://pub.dzne.de/record/162740 https://pub.dzne.de/search?p=id:%22DZNE-2021-01397%22 |
| Rights: | info:eu-repo/semantics/closedAccess |
| رقم الانضمام: | edsbas.4EAAE7D8 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |