دورية أكاديمية

Inhibition of the integrated stress response by viral proteins that block p-eIF2-eIF2B association

التفاصيل البيبلوغرافية
العنوان: Inhibition of the integrated stress response by viral proteins that block p-eIF2-eIF2B association
المؤلفون: Rabouw, Huib H, Visser, Linda J, Passchier, Tim C, Langereis, Martijn A, Liu, Fan, Giansanti, Piero, van Vliet, Arno L W, Dekker, José G, van der Grein, Susanne G, Saucedo, Jesús G, Anand, Aditya A, Trellet, Mikael E, Bonvin, Alexandre M J J, Walter, Peter, Heck, Albert J R, de Groot, Raoul J, van Kuppeveld, Frank J M
المساهمون: LS Virologie, dI&I I&I-1, Sub Biomol.Mass Spectrometry & Proteom., Virologie, dB&C I&I, Sub NMR Spectroscopy, Afd Biomol.Mass Spect. and Proteomics, Biomolecular Mass Spectrometry and Proteomics
سنة النشر: 2020
مصطلحات موضوعية: Taverne
الوصف: Eukaryotic cells, when exposed to environmental or internal stress, activate the integrated stress response (ISR) to restore homeostasis and promote cell survival. Specific stress stimuli prompt dedicated stress kinases to phosphorylate eukaryotic initiation factor 2 (eIF2). Phosphorylated eIF2 (p-eIF2) in turn sequesters the eIF2-specific guanine exchange factor eIF2B to block eIF2 recycling, thereby halting translation initiation and reducing global protein synthesis. To circumvent stress-induced translational shutdown, viruses encode ISR antagonists. Those identified so far prevent or reverse eIF2 phosphorylation. We now describe two viral proteins-one from a coronavirus and the other from a picornavirus-that have independently acquired the ability to counteract the ISR at its very core by acting as a competitive inhibitor of p-eIF2-eIF2B interaction. This allows continued formation of the eIF2-GTP-Met-tRNAi ternary complex and unabated global translation at high p-eIF2 levels that would otherwise cause translational arrest. We conclude that eIF2 and p-eIF2 differ in their interaction with eIF2B to such effect that p-eIF2-eIF2B association can be selectively inhibited.
نوع الوثيقة: article in journal/newspaper
وصف الملف: application/pdf
اللغة: English
تدمد: 1740-1526
العلاقة: https://dspace.library.uu.nl/handle/1874/408549Test
الإتاحة: https://dspace.library.uu.nl/handle/1874/408549Test
حقوق: info:eu-repo/semantics/OpenAccess
رقم الانضمام: edsbas.E786FBC6
قاعدة البيانات: BASE