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dc.contributor.authorHamid, S. M.
dc.contributor.authorÇıtır, M.
dc.contributor.authorTerzi, E. M.
dc.contributor.authorÇimen, İ.
dc.contributor.authorYıldırım, Zehra
dc.contributor.authorDoğan, Aslı Ekin
dc.contributor.authorKocatürk, B.
dc.contributor.authorOnat, Umut Inci
dc.contributor.authorArditi, M.
dc.contributor.authorWeber, C.
dc.contributor.authorTraynor‐Kaplan, A.
dc.contributor.authorSchultz, C.
dc.contributor.authorErbay, E.
dc.date.accessioned2021-02-28T21:30:49Z
dc.date.available2021-02-28T21:30:49Z
dc.date.issued2020-11
dc.identifier.issn1469-221X
dc.identifier.urihttp://hdl.handle.net/11693/75652
dc.description.abstractThe 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)P3) 5‐phosphatase‐2 (INPPL1) is a direct target of miR‐2137, which controls PI(3,4,5)P3 levels in macrophages. The modulation of cellular PI(3,4,5)P3/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.en_US
dc.language.isoEnglishen_US
dc.source.titleEMBO Reportsen_US
dc.relation.isversionofhttps://dx.doi.org/10.15252/embr.202051462en_US
dc.subjectER stressen_US
dc.subjectMicroRNAen_US
dc.subjectmTOR signalingen_US
dc.subjectHyperlipidemiaen_US
dc.subjectMacrophageen_US
dc.subjectSignal transductionen_US
dc.subjectRNAen_US
dc.subjectMolecular biology of diseaseen_US
dc.titleInositol‐requiring enzyme‐1 regulates phosphoinositide signaling lipids and macrophage growthen_US
dc.typeArticleen_US
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.departmentNanotechnology Research Center (NANOTAM)en_US
dc.citation.spagee51462en_US
dc.citation.volumeNumber21en_US
dc.citation.issueNumber12en_US
dc.identifier.doi10.15252/embr.202051462en_US
dc.publisherWiley-VCH Verlagen_US
dc.contributor.bilkentauthorYıldırım, Zehra
dc.contributor.bilkentauthorDoğan, Aslı Ekin
dc.contributor.bilkentauthorOnat, Umut Inci
dc.embargo.release2021-05-02


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