Inositol‐requiring enzyme‐1 regulates phosphoinositide signaling lipids and macrophage growth
| العنوان: | Inositol‐requiring enzyme‐1 regulates phosphoinositide signaling lipids and macrophage growth |
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| المؤلفون: | Begüm Kocatürk, Asli Ekin Dogan, Ebru Erbay, Zehra Yildirim, Ismail Çimen, Umut Inci Onat, Moshe Arditi, Christian Weber, Syed M. Hamid, Mevlut Citir, Carsten Schultz, Erdem M. Terzi, Alexis Traynor-Kaplan |
| المساهمون: | Biochemie, RS: Carim - B01 Blood proteins & engineering, Yıldırım, Zehra, Doğan, Aslı Ekin, Onat, Umut Inci |
| المصدر: | EMBO Rep Embo Reports, 21(12):51462. Wiley EMBO Reports |
| بيانات النشر: | John Wiley and Sons Inc., 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Macrophage, RNase P, Endoribonuclease, macrophage, Signal transduction, METABOLISM, Biochemistry, PATHWAY, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, ENDOPLASMIC-RETICULUM STRESS, Molecular biology of disease, Genetics, hyperlipidemia, CELL, Phosphatidylinositol, HEPATIC STEATOSIS, Molecular Biology, PI3K/AKT/mTOR pathway, 030304 developmental biology, 0303 health sciences, microRNA, UNFOLDED PROTEIN RESPONSE, Kinase, MTOR, RNA, MicroRNA, Articles, ER STRESS, Cell biology, Hyperlipidemia, MICRORNA TARGETS, ATHEROSCLEROSIS, chemistry, mTOR signaling, Unfolded protein response, ER stress, 030217 neurology & neurosurgery |
| الوصف: | The ER-bound kinase/endoribonuclease (RNase), inositol-requiring enzyme-1 (IRE1), regulates the phylogenetically most conserved arm of the unfolded protein response (UPR). However, the complex biology and pathology regulated by mammalian IRE1 cannot be fully explained by IRE1's one known, specific RNA target, X box-binding protein-1 (XBP1) or the RNA substrates of IRE1-dependent RNA degradation (RIDD) activity. Investigating other specific substrates of IRE1 kinase and RNase activities may illuminate how it performs these diverse functions in mammalian cells. We report that macrophage IRE1 plays an unprecedented role in regulating phosphatidylinositide-derived signaling lipid metabolites and has profound impact on the downstream signaling mediated by the mammalian target of rapamycin (mTOR). This cross-talk between UPR and mTOR pathways occurs through the unconventional maturation of microRNA (miR) 2137 by IRE1's RNase activity. Furthermore, phosphatidylinositol (3,4,5) phosphate (PI(3,4,5)P-3) 5-phosphatase-2 (INPPL1) is a direct target of miR-2137, which controls PI(3,4,5)P-3 levels in macrophages. The modulation of cellular PI(3,4,5)P-3/PIP2 ratio and anabolic mTOR signaling by the IRE1-induced miR-2137 demonstrates how the ER can provide a critical input into cell growth decisions. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1469-221X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::74faaeda4c2eb0aa52fde70f2b5fb996 https://europepmc.org/articles/PMC7726810/ |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....74faaeda4c2eb0aa52fde70f2b5fb996 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1469221X |
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