Gene Symbol: ERN1
Description: endoplasmic reticulum to nucleus signaling 1
Alias: IRE1, IRE1P, IRE1a, hIRE1p, serine/threonine-protein kinase/endoribonuclease IRE1, ER to nucleus signalling 1, inositol-requiring 1, inositol-requiring enzyme 1, inositol-requiring protein 1, ire1-alpha, protein kinase/endoribonuclease
Species: human
Products:     ERN1

Top Publications

  1. Oono K, Yoneda T, Manabe T, Yamagishi S, Matsuda S, Hitomi J, et al. JAB1 participates in unfolded protein responses by association and dissociation with IRE1. Neurochem Int. 2004;45:765-72 pubmed
    ..These results suggested that JAB1 may act as a key molecule in selecting the UPR or cell death by association and dissociation with IRE1alpha. ..
  2. Yoshida H, Matsui T, Yamamoto A, Okada T, Mori K. XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor. Cell. 2001;107:881-91 pubmed
    In yeast, the transmembrane protein kinase/endoribonuclease Ire1p activated by endoplasmic reticulum stress cleaves HAC1 mRNA, leading to production of the transcription factor Hac1p that activates the unfolded protein response (UPR)...
  3. Nishitoh H, Matsuzawa A, Tobiume K, Saegusa K, Takeda K, Inoue K, et al. ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death triggered by expanded polyglutamine repeats. Genes Dev. 2002;16:1345-55 pubmed
    ..length triggers ER stress through proteasomal dysfunction; (2) ER stress activates ASK 1 through formation of an IRE1-TRAF2-ASK1 complex; and (3) ASK1(-/-) primary neurons are defective in polyQ-, proteasome inhibitor-, and ER stress-..
  4. Tirasophon W, Welihinda A, Kaufman R. A stress response pathway from the endoplasmic reticulum to the nucleus requires a novel bifunctional protein kinase/endoribonuclease (Ire1p) in mammalian cells. Genes Dev. 1998;12:1812-24 pubmed
    ..The gene product hIre1p is a type 1 transmembrane protein containing a cytoplasmic domain that is highly conserved to the yeast ..
  5. Oikawa D, Tokuda M, Iwawaki T. Site-specific cleavage of CD59 mRNA by endoplasmic reticulum-localized ribonuclease, IRE1. Biochem Biophys Res Commun. 2007;360:122-7 pubmed
    b>IRE1, an ER-localized transmembrane-RNase, plays a central role in ER stress response. Upon ER stress, IRE1 induces various adaptive genes through the processing of mRNA encoding the transcription factor XBP1...
  6. Lisbona F, Rojas Rivera D, Thielen P, Zamorano S, Todd D, Martinon F, et al. BAX inhibitor-1 is a negative regulator of the ER stress sensor IRE1alpha. Mol Cell. 2009;33:679-91 pubmed publisher
    ..Our results suggest a role for BI-1 in early adaptive responses against ER stress that contrasts with its known downstream function in apoptosis. ..
  7. Gupta S, Deepti A, Deegan S, Lisbona F, Hetz C, Samali A. HSP72 protects cells from ER stress-induced apoptosis via enhancement of IRE1alpha-XBP1 signaling through a physical interaction. PLoS Biol. 2010;8:e1000410 pubmed publisher
    ..Our data show that binding of Hsp72 to IRE1alpha enhances IRE1alpha/XBP1 signaling at the ER and inhibits ER stress-induced apoptosis. These results provide a physical connection between cytosolic chaperones and the ER stress response. ..
  8. Auf G, Jabouille A, Guérit S, Pineau R, Delugin M, Bouchecareilh M, et al. Inositol-requiring enzyme 1alpha is a key regulator of angiogenesis and invasion in malignant glioma. Proc Natl Acad Sci U S A. 2010;107:15553-8 pubmed publisher
    Inositol-requiring enzyme 1 (IRE1) is a proximal endoplasmic reticulum (ER) stress sensor and a central mediator of the unfolded protein response...
  9. Woehlbier U, Hetz C. Modulating stress responses by the UPRosome: a matter of life and death. Trends Biochem Sci. 2011;36:329-37 pubmed publisher
    ..protein response (UPR) through the activation of specialized sensors including inositol-requiring enzyme-1? (IRE1?)...

More Information

Publications105 found, 100 shown here

  1. Lee H, Noh J, Oh Y, Kim Y, Chang J, Chung C, et al. IRE1 plays an essential role in ER stress-mediated aggregation of mutant huntingtin via the inhibition of autophagy flux. Hum Mol Genet. 2012;21:101-14 pubmed publisher
    ..mtHTT aggregation, we performed cell-based functional screening using the cDNA expression library and isolated IRE1 gene, one of endoplasmic reticulum (ER) stress sensors...
  2. Hassan I, Zhang M, Powers L, Shao J, Baltrusaitis J, Rutkowski D, et al. Influenza A viral replication is blocked by inhibition of the inositol-requiring enzyme 1 (IRE1) stress pathway. J Biol Chem. 2012;287:4679-89 pubmed publisher
    ..Influenza A virus induced ER stress in a pathway-specific manner. We showed that the virus activates the IRE1 pathway with little or no concomitant activation of the PERK and the ATF6 pathways...
  3. Cross B, Bond P, Sadowski P, Jha B, Zak J, Goodman J, et al. The molecular basis for selective inhibition of unconventional mRNA splicing by an IRE1-binding small molecule. Proc Natl Acad Sci U S A. 2012;109:E869-78 pubmed publisher
    b>IRE1 couples endoplasmic reticulum unfolded protein load to RNA cleavage events that culminate in the sequence-specific splicing of the Xbp1 mRNA and in the regulated degradation of diverse membrane-bound mRNAs...
  4. Zheng Q, Li P, Jin F, Yao C, Zhang G, Zang T, et al. Ursolic acid induces ER stress response to activate ASK1-JNK signaling and induce apoptosis in human bladder cancer T24 cells. Cell Signal. 2013;25:206-13 pubmed publisher
    ..Ursolic acid induces IRE1-TRAF2-ASK1 signaling complex formation to activate pro-apoptotic ASK1-JNK signaling...
  5. Upton J, Wang L, Han D, Wang E, Huskey N, Lim L, et al. IRE1? cleaves select microRNAs during ER stress to derepress translation of proapoptotic Caspase-2. Science. 2012;338:818-22 pubmed publisher
    ..Inability to meet protein-folding demand leads to "ER stress," and activates IRE1?, an ER transmembrane kinase-endoribonuclease (RNase)...
  6. Urano F, Wang X, Bertolotti A, Zhang Y, Chung P, Harding H, et al. Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1. Science. 2000;287:664-6 pubmed
    ..Mammalian homologs of yeast IRE1, which activate chaperone genes in response to ER stress, also activated JNK, and IRE1alpha-/- fibroblasts were ..
  7. Yoneda T, Imaizumi K, Oono K, Yui D, Gomi F, Katayama T, et al. Activation of caspase-12, an endoplastic reticulum (ER) resident caspase, through tumor necrosis factor receptor-associated factor 2-dependent mechanism in response to the ER stress. J Biol Chem. 2001;276:13935-40 pubmed
    ..Thus, we provide a missing link in the ER stress-induced apoptosis-signaling pathway, one which connects the stress sensor molecule IRE1 and the activation of caspase-12.
  8. Shen X, Ellis R, Lee K, Liu C, Yang K, Solomon A, et al. Complementary signaling pathways regulate the unfolded protein response and are required for C. elegans development. Cell. 2001;107:893-903 pubmed
    ..We propose that UPR transcriptional activation by ire-1 as well as translational attenuation by pek-1 maintain ER homeostasis. The results demonstrate that the UPR and ER homeostasis are essential for metazoan development. ..
  9. Lee K, Tirasophon W, Shen X, Michalak M, Prywes R, Okada T, et al. IRE1-mediated unconventional mRNA splicing and S2P-mediated ATF6 cleavage merge to regulate XBP1 in signaling the unfolded protein response. Genes Dev. 2002;16:452-66 pubmed
    ..In yeast, a type-I ER transmembrane protein kinase, Ire1p, is the proximal sensor of unfolded proteins in the ER lumen that initiates an unconventional splicing reaction on ..
  10. Marcu M, Doyle M, Bertolotti A, Ron D, Hendershot L, Neckers L. Heat shock protein 90 modulates the unfolded protein response by stabilizing IRE1alpha. Mol Cell Biol. 2002;22:8506-13 pubmed
    ..These data establish a role for HSP90 in the cellular transcriptional response to ER stress and demonstrate that chaperone systems on both sides of the ER membrane serve to integrate this signal transduction cascade. ..
  11. Hetz C, Bernasconi P, Fisher J, Lee A, Bassik M, Antonsson B, et al. Proapoptotic BAX and BAK modulate the unfolded protein response by a direct interaction with IRE1alpha. Science. 2006;312:572-6 pubmed tunicamycin-induced ER stress in the liver, with extensive tissue damage and decreased expression of the IRE1 substrate X-box-binding protein 1 and its target genes. ER-stressed DKO cells showed deficient IRE1alpha signaling...
  12. Gao B, Lee S, Chen A, Zhang J, Zhang D, Kannan K, et al. Synoviolin promotes IRE1 ubiquitination and degradation in synovial fibroblasts from mice with collagen-induced arthritis. EMBO Rep. 2008;9:480-5 pubmed publisher that elevated SYVN1 expression correlates with decreased levels of the protein inositol-requiring enzyme 1 (IRE1)-a pro-apoptotic factor in the endoplasmic reticulum (ER)-stress-induced apoptosis pathway-in synovial fibroblasts ..
  13. Li H, Korennykh A, Behrman S, Walter P. Mammalian endoplasmic reticulum stress sensor IRE1 signals by dynamic clustering. Proc Natl Acad Sci U S A. 2010;107:16113-8 pubmed publisher
    ..The ER-resident transmembrane kinase-endoribonuclease inositol-requiring enzyme 1 (IRE1) is the best characterized UPR signal transduction molecule...
  14. Ali M, Bagratuni T, Davenport E, Nowak P, Silva Santisteban M, Hardcastle A, et al. Structure of the Ire1 autophosphorylation complex and implications for the unfolded protein response. EMBO J. 2011;30:894-905 pubmed publisher
    b>Ire1 (Ern1) is an unusual transmembrane protein kinase essential for the endoplasmic reticulum (ER) unfolded protein response (UPR)...
  15. Lin J, Li H, Yasumura D, Cohen H, Zhang C, Panning B, et al. IRE1 signaling affects cell fate during the unfolded protein response. Science. 2007;318:944-9 pubmed
    ..The three UPR branches (IRE1, PERK, and ATF6) promote cell survival by reducing misfolded protein levels...
  16. Gao P, Yang B, Yu H, Meng R, Si J. Carvedilol alleviates the biliary cirrhosis through inhibiting the endoplasmic reticulum stress. Eur Rev Med Pharmacol Sci. 2017;21:5813-5820 pubmed publisher
    ..protein homologous protein), activating transcription factor 4 (ATF4), ATF6, inositol-requiring enzyme 1 (IRE1), phosphorylated Jun N-terminal kinase (pJNK), ?-SMA, and collagen-1, were detected via Western-blotting...
  17. Chen J, Hou X, Wang G, Zhong Q, Liu Y, Qiu H, et al. Terpene glycoside component from Moutan Cortex ameliorates diabetic nephropathy by regulating endoplasmic reticulum stress-related inflammatory responses. J Ethnopharmacol. 2016;193:433-444 pubmed publisher
    ..cell adhesion molecule-1 (ICAM-1), GRP78/Bip, XBP-1 (s), phosphorylated inositol-requiring enzyme-1? (p-IRE1?), cleaved activating transcription factor 6 (ATF6), phosphorylated PKR-like endoplasmic reticulum kinase (p-PERK), ..
  18. Wen L, Han F, Shi Y, Li X. Role of the Endoplasmic Reticulum Pathway in the Medial Prefrontal Cortex in Post-Traumatic Stress Disorder Model Rats. J Mol Neurosci. 2016;59:471-82 pubmed publisher
    ..eukaryotic translation initiation factor 2A (p-eIF2a), ATF6a/X-box binding protein 1 (XBP1), and IRE1a. In addition, the ER molecular chaperone 78-kDa glucose-regulated protein (GRP78) and the ER-related apoptosis ..
  19. Wang J, Zuo X, Xu J, Zhou J, Kong H, Zeng X, et al. Evaluation and Treatment of Endoplasmic Reticulum (ER) Stress in Right Ventricular Dysfunction during Monocrotaline-Induced Rat Pulmonary Arterial Hypertension. Cardiovasc Drugs Ther. 2016;30:587-598 pubmed
    ..78 (GRP78), three ER stress sensor proteins: activating transcription factor 6 (ATF6), inositol-requiring enzyme 1 (IRE1), and protein kinase RNA-like endoplasmic reticulum kinase (PERK), and a key ER stress-induced apoptosis indicator: ..
  20. Camargo L, Harvey A, Rios F, Tsiropoulou S, Da Silva R, Cao Z, et al. Vascular Nox (NADPH Oxidase) Compartmentalization, Protein Hyperoxidation, and Endoplasmic Reticulum Stress Response in Hypertension. Hypertension. 2018;72:235-246 pubmed publisher
    ..phosphatase, peroxiredoxin oxidation), and ER stress (PERK [protein kinase RNA-like endoplasmic reticulum kinase], IRE1α [inositol-requiring enzyme 1], and phosphorylation/oxidation) were studied in spontaneously hypertensive rat (SHR)..
  21. Kobylewski S, Henderson K, Yamada K, Eckhert C. Activation of the EIF2α/ATF4 and ATF6 Pathways in DU-145 Cells by Boric Acid at the Concentration Reported in Men at the US Mean Boron Intake. Biol Trace Elem Res. 2017;176:278-293 pubmed publisher
    ..BA did not activate IRE1 or induce cleavage of XBP1 mRNA, a target of IRE1...
  22. Yao X, Li Y, Cheng X, Li H. ER stress contributes to alpha-naphthyl isothiocyanate-induced liver injury with cholestasis in mice. Pathol Res Pract. 2016;212:560-7 pubmed publisher
    ..ANIT also upregulated the protein expression of GRP78 and activated the phosphorylation of IRE1. These results suggested that ANIT induced liver injury with cholestasis partly due to its ability to activate the ..
  23. Sangüesa G, Montañés J, Baena M, Sánchez R, Roglans N, Alegret M, et al. Chronic fructose intake does not induce liver steatosis and inflammation in female Sprague-Dawley rats, but causes hypertriglyceridemia related to decreased VLDL receptor expression. Eur J Nutr. 2018;: pubmed publisher
    ..reduced liver expression of gluconeogenic enzymes, despite both sugars increased fatty acid synthesis, mTORC1, and IRE1 activity, while decreasing fatty acid oxidation and PPARα activity...
  24. Biazi B, Zanetti T, Baranoski A, Corveloni A, Mantovani M. Cis-Nerolidol Induces Endoplasmic Reticulum Stress and Cell Death in Human Hepatocellular Carcinoma Cells through Extensive CYP2C19 and CYP1A2 Oxidation. Basic Clin Pharmacol Toxicol. 2017;121:334-341 pubmed publisher
    ..seen in case of genes related to cell survival (BBC3 and MYC) and reticulum stress protein response (EIF2AK3 and ERN1) and xenobiotic metabolism (CYP1A2 and CYP2C19)...
  25. Liu G, Wang K, Guo H, Zhao S, Shen Y, Zhao Y. Inositol-requiring protein 1? signaling pathway is activated in the temporal cortex of patients with mesial temporal lobe epilepsy. Neurol Sci. 2013;34:357-64 pubmed publisher
    ..Inositol-requiring protein 1? (IRE1?) is a vital pro-apoptotic molecule in ER stress, but it remains unclear whether the signaling pathway mediated by ..
  26. Minchenko O, Garmash I, Kovalevska O, Tsymbal D, Minchenko D. Expression of phosphoribosyl pyrophosphate synthetase genes in U87 glioma cells with ERN1 knockdown: effect of hypoxia and endoplasmic reticulum stress. Ukr Biochem J. 2014;86:74-83 pubmed
    ..Hypoxia as well as ERN1 (from endoplasmic reticulum to nuclei-1) mediated endoplasmic reticulum stress response-signalling pathway is ..
  27. Liu D, Liu X, Zhou T, Yao W, Zhao J, Zheng Z, et al. IRE1-RACK1 axis orchestrates ER stress preconditioning-elicited cytoprotection from ischemia/reperfusion injury in liver. J Mol Cell Biol. 2016;8:144-56 pubmed publisher administration of tunicamycin, which induced ER stress in rat liver by activating inositol-requiring enzyme 1 (IRE1) and upregulating 78 kDa glucose-regulated protein (GRP78)...
  28. Qie X, Wen D, Guo H, Xu G, Liu S, Shen Q, et al. Endoplasmic Reticulum Stress Mediates Methamphetamine-Induced Blood-Brain Barrier Damage. Front Pharmacol. 2017;8:639 pubmed publisher
    ..METH activated ER stress sensor proteins, including PERK, ATF6, and IRE1, and upregulated the pro-apoptotic protein CHOP...
  29. Tang C, Chang S, Paton A, Paton J, Gabrilovich D, Ploegh H, et al. Phosphorylation of IRE1 at S729 regulates RIDD in B cells and antibody production after immunization. J Cell Biol. 2018;217:1739-1755 pubmed publisher
    To relieve endoplasmic reticulum (ER) stress, IRE1 splices XBP1 messenger RNA (mRNA) or engages regulated IRE1-dependent decay (RIDD) of other mRNAs. Upon XBP1 deficiency, IRE1 switches to perform RIDD...
  30. Hsieh Y, Su I, Wang H, Tsai J, Huang Y, Chang W, et al. Hepatitis B virus pre-S2 mutant surface antigen induces degradation of cyclin-dependent kinase inhibitor p27Kip1 through c-Jun activation domain-binding protein 1. Mol Cancer Res. 2007;5:1063-72 pubmed publisher
    ..Association of pre-S(2) LHBS with JAB1 dissociated JAB1 from the JAB1/IRE1 complex in ER...
  31. Chiang W, Messah C, Lin J. IRE1 directs proteasomal and lysosomal degradation of misfolded rhodopsin. Mol Biol Cell. 2012;23:758-70 pubmed publisher
    ..Inositol-requiring enzyme 1 (IRE1) directs a key unfolded protein response signaling pathway that controls the fidelity of ER protein folding...
  32. Tomasio S, Harding H, Ron D, Cross B, Bond P. Selective inhibition of the unfolded protein response: targeting catalytic sites for Schiff base modification. Mol Biosyst. 2013;9:2408-16 pubmed publisher
    ..In particular, the most ancient component of this cellular stress pathway, the transmembrane protein IRE1, represents an appealing target for pharmacological intervention...
  33. Fusakio M, Willy J, Wang Y, Mirek E, Al Baghdadi R, Adams C, et al. Transcription factor ATF4 directs basal and stress-induced gene expression in the unfolded protein response and cholesterol metabolism in the liver. Mol Biol Cell. 2016;27:1536-51 pubmed publisher
    ..Each of three UPR sensory proteins-PERK (PEK/EIF2AK3), IRE1, and ATF6-is activated by ER stress...
  34. Cubillos Ruiz J, Bettigole S, Glimcher L. Molecular Pathways: Immunosuppressive Roles of IRE1?-XBP1 Signaling in Dendritic Cells of the Tumor Microenvironment. Clin Cancer Res. 2016;22:2121-6 pubmed publisher
    ..Cancer cells exploit the IRE1?-XBP1 arm of the ER stress response to efficiently adjust their protein-folding capacity and ensure survival under ..
  35. Cerri M, Frances L, Kelner A, Fournier J, Middleton P, Auriac M, et al. The Symbiosis-Related ERN Transcription Factors Act in Concert to Coordinate Rhizobial Host Root Infection. Plant Physiol. 2016;171:1037-54 pubmed publisher
    ..infection of legumes is regulated by a number of transcription factors, including ERF Required for Nodulation1 (ERN1)...
  36. Wu C, Lee M, El Shazly M, Lai K, Ke S, Su C, et al. Isoaaptamine Induces T-47D Cells Apoptosis and Autophagy via Oxidative Stress. Mar Drugs. 2018;16: pubmed publisher
    ..In addition, isoaaptamine treatment enhanced the activation of DNA damage (?H2AX) and ER stress-related proteins (IRE1 ? and BiP)...
  37. Chen J, Zhang M, Zhu M, Gu J, Song J, Cui L, et al. Paeoniflorin prevents endoplasmic reticulum stress-associated inflammation in lipopolysaccharide-stimulated human umbilical vein endothelial cells via the IRE1α/NF-κB signaling pathway. Food Funct. 2018;9:2386-2397 pubmed publisher
    ..Impressively, we find that the inositol-requiring enzyme 1α (IRE1α)/nuclear factor-kappa B (NF-κB) pathway is significantly activated and contributes to the progress of LPS-..
  38. Estornes Y, Aguileta M, Dubuisson C, De Keyser J, Goossens V, Kersse K, et al. RIPK1 promotes death receptor-independent caspase-8-mediated apoptosis under unresolved ER stress conditions. Cell Death Dis. 2014;5:e1555 pubmed publisher
    ..Our data rather suggest that RIPK1 indirectly regulates caspase-8 activation, in part via interaction with the ER stress sensor inositol-requiring protein 1 (IRE1).
  39. Mo X, Zhou W, Cui W, Li D, Li L, Xu L, et al. Inositol-requiring protein 1 - X-box-binding protein 1 pathway promotes epithelial-mesenchymal transition via mediating snail expression in pulmonary fibrosis. Int J Biochem Cell Biol. 2015;65:230-8 pubmed publisher
    ..experiments in alveolar epithelial cell (AECs) RLE-6TN to unravel the role of inositol-requiring protein 1 (IRE1) - X-box-binding protein 1 (XBP1) signal pathway in ER stress-induced EMT in PF...
  40. Chan J, Luzuriaga J, Maxwell E, West P, Bensellam M, Laybutt D. The balance between adaptive and apoptotic unfolded protein responses regulates β-cell death under ER stress conditions through XBP1, CHOP and JNK. Mol Cell Endocrinol. 2015;413:189-201 pubmed publisher
    ..This response was prevented by CHOP inhibition. IRE1/XBP1 inhibition led to alterations in islets from diabetes-resistant ob/ob mice that resemble those found in ..
  41. Zheng X, Jin X, Li F, Liu X, Liu Y, Ye F, et al. Inhibiting autophagy with chloroquine enhances the anti-tumor effect of high-LET carbon ions via ER stress-related apoptosis. Med Oncol. 2017;34:25 pubmed publisher
    ..Co-treatment with CI radiation and CQ could block autophagy through the IRE1/JNK/Beclin-1 axis and enhance apoptotic cell death via the activation of C/EBP homologous protein (CHOP) by the ..
  42. Li X, He X, Zhou Y, Zhao H, Zheng W, Jiang S, et al. Taraxacum mongolicum extract induced endoplasmic reticulum stress associated-apoptosis in triple-negative breast cancer cells. J Ethnopharmacol. 2017;206:55-64 pubmed publisher
    ..expressions of ATF4, ATF6, XBP1s, GRP78 and CHOP genes, elevated protein levels of phosphorylated PERK, eIF-2α, IRE1, as well as the downstream molecules of CHOP and GRP78...
  43. Kono N, Amin Wetzel N, Ron D. Generic membrane-spanning features endow IRE1? with responsiveness to membrane aberrancy. Mol Biol Cell. 2017;28:2318-2332 pubmed publisher
    ..We used CRISPR/Cas9-mediated gene editing of the Ern1 locus to study the role of the TMD in the ability of the endogenous IRE1? protein to recognize membrane ..
  44. Su A, Wang H, Li Y, Wang X, Chen D, Wu Z. Opposite Roles of RNase and Kinase Activities of Inositol-Requiring Enzyme 1 (IRE1) on HSV-1 Replication. Viruses. 2017;9: pubmed publisher
    ..UPR has three branches, including protein kinase RNA (PKR)-like ER kinase (PERK), inositol-requiring enzyme 1 (IRE1), and activated transcription factor 6 (ATF6)...
  45. Saito A, Cai L, Matsuhisa K, Ohtake Y, Kaneko M, Kanemoto S, et al. Neuronal activity-dependent local activation of dendritic unfolded protein response promotes expression of brain-derived neurotrophic factor in cell soma. J Neurochem. 2018;144:35-49 pubmed publisher
    ..ER stress transducer, inositol-requiring kinase 1 (IRE1), was activated at postsynapses in response to excitatory synaptic activation...
  46. Singh M, Kang S. Endoplasmic reticulum stress-mediated autophagy activation attenuates fumonisin B1 induced hepatotoxicity in vitro and in vivo. Food Chem Toxicol. 2017;110:371-382 pubmed publisher
    ..Moreover, the expression levels of major ER stress and autophagy-related markers such as PERK, IRE1-?, and LC3I/II also increased...
  47. Minchenko O, Riabovol O, Tsymbal D, Minchenko D, Ratushna O. Effect of hypoxia on the expression of nuclear genes encoding mitochondrial proteins in U87 glioma cells. Ukr Biochem J. 2016;88:54-65 pubmed publisher
    ..on the expression of nuclear genes encoding mitochondrial proteins in U87 glioma cells under the inhibition of IRE1 (inositol requiring enzyme-1), which controls cell proliferation and tumor growth as a central mediator of ..
  48. Wang Z, Liu N, Shi T, Zhou G, Wang Z, Gan J, et al. ER Stress Mediates TiAl6V4 Particle-Induced Peri-Implant Osteolysis by Promoting RANKL Expression in Fibroblasts. PLoS ONE. 2015;10:e0137774 pubmed publisher
    ..The expression of ER stress markers, including IRE1-α, GRP78/Bip and CHOP, were determined by western blot in fibroblasts that had been treated with TiPs for ..
  49. Shah A, Vaidya N, Bhat H, Kumar A. HIV-1 gp120 induces type-1 programmed cell death through ER stress employing IRE1α, JNK and AP-1 pathway. Sci Rep. 2016;6:18929 pubmed publisher
    ..The present study was undertaken to assess the involvement and detailed mechanism of IRE1α pathway in HIV-1 gp120-mediated ER stress and its possible involvement in cell death...
  50. Ruwan Kumara M, Piao M, Kang K, Ryu Y, Park J, Shilnikova K, et al. Non-thermal gas plasma-induced endoplasmic reticulum stress mediates apoptosis in human colon cancer cells. Oncol Rep. 2016;36:2268-74 pubmed publisher
    ..protein 78 (GRP78), protein kinase R (PKR)?like ER kinase (PERK), and inositol?requiring enzyme 1 (IRE1)...
  51. Tang J, Jin P, He Q, Lu L, Ma J, Gao W, et al. Naringenin ameliorates hypoxia/reoxygenation-induced endoplasmic reticulum stress-mediated apoptosis in H9c2 myocardial cells: involvement in ATF6, IRE1? and PERK signaling activation. Mol Cell Biochem. 2017;424:111-122 pubmed publisher
    ..phosphorylation levels of phospho-extracellular regulated protein kinases (PERK) and inositol-requiring enzyme-1? (IRE1?) in H9c2 cells...
  52. Rozpedek W, Nowak A, Pytel D, Diehl J, Majsterek I. Molecular Basis of Human Diseases and Targeted Therapy Based on Small-Molecule Inhibitors of ER Stress-Induced Signaling Pathways. Curr Mol Med. 2017;17:118-132 pubmed publisher
    ..receptors of impaired protein folding: Protein kinase RNA (PKR)-like ER kinase (PERK), Inositol-requiring enzyme-1 (IRE1) and Activating transcription factor 6 (ATF6)...
  53. Pillon M, Sobhany M, Borgnia M, Williams J, Stanley R. Grc3 programs the essential endoribonuclease Las1 for specific RNA cleavage. Proc Natl Acad Sci U S A. 2017;114:E5530-E5538 pubmed publisher
    ..The tetrameric Grc3/Las1 cross talk draws unexpected parallels to endoribonucleases RNaseL and Ire1, and establishes Grc3/Las1 as a unique member of the RNaseL/Ire1 RNA splicing family...
  54. Zhang Y, Li S, Li J, Han L, He Q, Wang R, et al. Developmental toxicity induced by PM2.5 through endoplasmic reticulum stress and autophagy pathway in zebrafish embryos. Chemosphere. 2018;197:611-621 pubmed publisher
    ..RT-PCR showed that the expression of genes related to inflammation (tgf? and cox2), ERS (hspa5, chop, ire1, xbp1s, and atf6) and autophagy (lc3, beclin1 and atg3) pathways was significantly increased in the PM2...
  55. Tsymbal D, Minchenko D, Kryvdiuk I, Riabovo O, Halkin O, Ratushna O, et al. Expression of proliferation related transcription factor genes in U87 glioma cells with IRE1 knockdown: upon glucose and glutamine deprivation. Fiziol Zh. 2016;62:3-15 pubmed
    ..Inhibition of ERN1/IRE1 (endoplasmic reticulum to nucleus signaling 1/inositol requiring enzyme 1), a central mediator of endoplasmic reticulum stress, significantly suppresses glioma cell ..
  56. Fan X, Weng Y, Bai Y, Wang Z, Wang S, Zhu J, et al. Lipin-1 determines lung cancer cell survival and chemotherapy sensitivity by regulation of endoplasmic reticulum homeostasis and autophagy. Cancer Med. 2018;7:2541-2554 pubmed publisher
    ..Lipin-1 silencing induces the activation of ER stress through the IRE1? pathway...
  57. Norisada J, Fujimura K, Amaya F, Kohno H, Hirata Y, Oh hashi K. Application of NanoBiT for Monitoring Dimerization of the Null Hong Kong Variant of α-1-Antitrypsin, NHK, in Living Cells. Mol Biotechnol. 2018;60:539-549 pubmed publisher
    ..We then focused on mesencephalic astrocyte-derived neurotrophic factor (MANF), an unclarified ATF6/IRE1-downstream target, and established MANF-deficient Neuro2a (N2a) cells using CRISPR/Cas9 system...
  58. Nakato R, Ohkubo Y, Konishi A, Shibata M, Kaneko Y, Iwawaki T, et al. Regulation of the unfolded protein response via S-nitrosylation of sensors of endoplasmic reticulum stress. Sci Rep. 2015;5:14812 pubmed publisher
    ..We demonstrate that nitric oxide (NO) can S-nitrosylate the ER stress sensors IRE1α and PERK...
  59. Leclerc D, Rozen R. Endoplasmic reticulum stress increases the expression of methylenetetrahydrofolate reductase through the IRE1 transducer. J Biol Chem. 2008;283:3151-60 pubmed
    ..The induction of MTHFR was also observed after overexpression of inositol-requiring enzyme-1 (IRE1) and was inhibited by a dominant-negative mutant of IRE1...
  60. Sou S, Ilieva K, Polizzi K. Binding of human BiP to the ER stress transducers IRE1 and PERK requires ATP. Biochem Biophys Res Commun. 2012;420:473-8 pubmed publisher
    ..ATP, but not ADP, was required to isolate the BiP-IRE1 and the BiP-PERK complexes, but the BiP-ATF6 complex was purified in all conditions tested...
  61. Pehar M, Jonas M, Hare T, Puglielli L. SLC33A1/AT-1 protein regulates the induction of autophagy downstream of IRE1/XBP1 pathway. J Biol Chem. 2012;287:29921-30 pubmed publisher
    ..Here we show that IRE1/XBP1 controls the induction of autophagy/ERAD(II) during the unfolded protein response by activating the ER ..
  62. Prola A, Pires Da Silva J, Guilbert A, Lecru L, Piquereau J, Ribeiro M, et al. SIRT1 protects the heart from ER stress-induced cell death through eIF2α deacetylation. Cell Death Differ. 2017;24:343-356 pubmed publisher
    ..e., PERK/eIF2α, ATF6 and IRE1) showed that SIRT1 protects cardiomyocytes from ER stress-induced apoptosis by attenuating PERK/eIF2α pathway ..
  63. Ma Z, Yang Y, Di S, Feng X, Liu D, Jiang S, et al. Pterostilbene exerts anticancer activity on non-small-cell lung cancer via activating endoplasmic reticulum stress. Sci Rep. 2017;7:8091 pubmed publisher
    ..e., p-PERK, IRE1, ATF4, CHOP), thus decreasing the cell viability and inducing apoptosis in human PC9 and A549 NSCLC cell lines...
  64. Iwawaki T, Hosoda A, Okuda T, Kamigori Y, Nomura Furuwatari C, Kimata Y, et al. Translational control by the ER transmembrane kinase/ribonuclease IRE1 under ER stress. Nat Cell Biol. 2001;3:158-64 pubmed
    ..The evidence suggests that both pathways are important for efficient translational repression during the ER stress response. ..
  65. Uemura A, Oku M, Mori K, Yoshida H. Unconventional splicing of XBP1 mRNA occurs in the cytoplasm during the mammalian unfolded protein response. J Cell Sci. 2009;122:2877-86 pubmed publisher
    ..Its expression is regulated by unconventional mRNA splicing that is carried out by endonuclease IRE1 and a specific, as yet unknown, RNA ligase in response to the accumulation of unfolded proteins in the ER...
  66. Dai K, Khatun I, Hussain M. NR2F1 and IRE1beta suppress microsomal triglyceride transfer protein expression and lipoprotein assembly in undifferentiated intestinal epithelial cells. Arterioscler Thromb Vasc Biol. 2010;30:568-74 pubmed publisher
    ..We propose that transcriptional and posttranscriptional mechanisms involving NR2F1 and IRE1beta ensure low MTP expression in undifferentiated intestinal cells and avoid apolipoprotein B lipoprotein biosynthesis. ..
  67. Itzhak D, Bright M, McAndrew P, Mirza A, Newbatt Y, Strover J, et al. Multiple autophosphorylations significantly enhance the endoribonuclease activity of human inositol requiring enzyme 1?. BMC Biochem. 2014;15:3 pubmed publisher
    ..stress, caused by the presence of misfolded proteins, activates the stress sensor inositol-requiring enzyme 1? (IRE1?)...
  68. Fung T, Liao Y, Liu D. The endoplasmic reticulum stress sensor IRE1α protects cells from apoptosis induced by the coronavirus infectious bronchitis virus. J Virol. 2014;88:12752-64 pubmed publisher
    ..that in cells infected with the avian coronavirus infectious bronchitis virus (IBV), ER stress was induced and the IRE1α-XBP1 pathway of UPR was activated...
  69. Taguchi Y, Imaoka K, Kataoka M, Uda A, Nakatsu D, Horii Okazaki S, et al. Yip1A, a novel host factor for the activation of the IRE1 pathway of the unfolded protein response during Brucella infection. PLoS Pathog. 2015;11:e1004747 pubmed publisher
    ..abortus acquires the ER-derived membrane. First, during Brucella infection, the IRE1 pathway, but not the PERK and ATF6 pathways, of the unfolded protein response (UPR) was activated in a time-..
  70. Kryvdiuk I, Minchenko D, Hlushchak N, Ratushna O, Karbovskyi L, Minchenko O. INHIBITION OF IRE1 MODIFIES EFFECT OF GLUCOSE DEPRIVATION ON THE EXPRESSION OF TNF?-RELATED GENES IN U87 GLIOMA CELLS. Ukr Biochem J. 2015;87:36-51 pubmed
    Inhibition of IRE1 (inositol requiring enzyme-1), the major signaling pathway of endoplasmic reticulm stress, significantly decreases glioma cell proliferation and tumor growth...
  71. Páez Franco J, González Sánchez I, Gutierrez Najera N, Valencia Turcotte L, Lira Rocha A, Cerbón M, et al. Proteomic Profiling Reveals the Induction of UPR in Addition to DNA Damage Response in HeLa Cells Treated With the Thiazolo[5,4-b]Quinoline Derivative D3ClP. J Cell Biochem. 2017;118:1164-1173 pubmed publisher
    ..The IRE1-? dependent splicing of mRNA encoding X-box binding protein 1 was detected...
  72. Minchenko D, Riabovol O, Ratushna O, Minchenko O. Hypoxic regulation of the expression of genes encoded estrogen related proteins in U87 glioma cells: eff ect of IRE1 inhibition. Endocr Regul. 2017;51:8-19 pubmed publisher
    ..was to examine the effect of inhibition of endoplasmic reticulum stress signaling, mediated by IRE1 (inositol requiring enzyme 1), which is a central mediator of the unfolded protein response on the expression of genes encoded ..
  73. Duran Aniotz C, Cornejo V, Espinoza S, Ardiles A, Medinas D, Salazar C, et al. IRE1 signaling exacerbates Alzheimer's disease pathogenesis. Acta Neuropathol. 2017;134:489-506 pubmed publisher
    ..b>IRE1 is an ER-located kinase and endoribonuclease that operates as a major stress transducer, mediating both adaptive ..
  74. Huang H, Zeng X, Rhim T, Ron D, Ryoo H. The requirement of IRE1 and XBP1 in resolving physiological stress during Drosophila development. J Cell Sci. 2017;130:3040-3049 pubmed publisher
    b>IRE1 mediates the unfolded protein response (UPR) in part by regulating XBP1 mRNA splicing in response to endoplasmic reticulum (ER) stress. In cultured metazoan cells, IRE1 also exhibits XBP1-independent biochemical activities...
  75. Prentice H, Pan C, Gharibani P, Ma Z, Price A, Giraldo G, et al. Analysis of Neuroprotection by Taurine and Taurine Combinations in Primary Neuronal Cultures and in Neuronal Cell Lines Exposed to Glutamate Excitotoxicity and to Hypoxia/Re-oxygenation. Adv Exp Med Biol. 2017;975 Pt 1:207-216 pubmed publisher
    ..stress pathways we demonstrated that taurine treatment can result in reduced levels of cleaved ATF6 and decreased p-IRE1 levels. We hypothesized that because of the complex nature of stroke a combination therapy approach may be optimal...
  76. Yang Q, Kim Y, Lin Y, Lewis J, Neckers L, Liu Z. Tumour necrosis factor receptor 1 mediates endoplasmic reticulum stress-induced activation of the MAP kinase JNK. EMBO Rep. 2006;7:622-7 pubmed
    ..We also found that TNFR1 functions downstream of IRE1 and that IRE1 is present in the same complex with TNFR1 under ER stress condition...
  77. Yanagisawa K, Konishi H, Arima C, Tomida S, Takeuchi T, Shimada Y, et al. Novel metastasis-related gene CIM functions in the regulation of multiple cellular stress-response pathways. Cancer Res. 2010;70:9949-58 pubmed publisher
  78. Tam A, Mercado E, Hoffmann A, Niwa M. ER stress activates NF-?B by integrating functions of basal IKK activity, IRE1 and PERK. PLoS ONE. 2012;7:e45078 pubmed publisher
    ..Furthermore, a key UPR initiator, IRE1, acts to maintain IKK basal activity through IRE1's kinase, but not RNase, activity...
  79. Qiu Q, Zheng Z, Chang L, Zhao Y, Tan C, Dandekar A, et al. Toll-like receptor-mediated IRE1? activation as a therapeutic target for inflammatory arthritis. EMBO J. 2013;32:2477-90 pubmed publisher
    ..synovial fluid of RA patients and observed a significant increase in activation of inositol-requiring enzyme 1? (IRE1?), a primary unfolded protein response (UPR) transducer...
  80. Deegan S, Koryga I, Glynn S, Gupta S, Gorman A, Samali A. A close connection between the PERK and IRE arms of the UPR and the transcriptional regulation of autophagy. Biochem Biophys Res Commun. 2015;456:305-11 pubmed publisher
    ..the transcriptional upregulation of the autophagy receptor genes SQSTM1/p62, NBR1 and BNIP3L/NIX in response to ER stress and show that the inhibition of the UPR transmembrane receptors, PERK and IRE1, abrogates this upregulation.
  81. Minchenko O, Tsymbal D, Minchenko D, Kovalevska O, Karbovskyi L, Bikfalvi A. INHIBITION OF ERN1 SIGNALING ENZYME AFFECTS HYPOXIC REGULATION OF THE EXPRESSION OF E2F8, EPAS1, HOXC6, ATF3, TBX3 AND FOXF1 GENES IN U87 GLIOMA CELLS. Ukr Biochem J. 2015;87:76-87 pubmed
    ..Furthermore, blockade of ERN1 (endoplasmic reticulum to nucleus 1) suppresses cell proliferation and tumor growth...
  82. Zeng L, Li Y, Yang J, Wang G, Margariti A, Xiao Q, et al. XBP 1-Deficiency Abrogates Neointimal Lesion of Injured Vessels Via Cross Talk With the PDGF Signaling. Arterioscler Thromb Vasc Biol. 2015;35:2134-44 pubmed publisher
    ..This study demonstrates for the first time that XBP1 is crucial for SMC proliferation via modulating the platelet-derived growth factor/TGF-β pathways, leading to neointimal formation. ..
  83. Xu X, Liu J, Huang B, Chen M, Yuan S, Li X, et al. Reduced response of IRE1?/Xbp-1 signaling pathway to bortezomib contributes to drug resistance in multiple myeloma cells. Tumori. 2017;103:261-267 pubmed publisher
    ..We aimed to investigate the role of IRE1?/Xbp-1 mediated branch of the UPR in bortezomib resistance...
  84. Sakatani T, Maemura K, Hiyama N, Amano Y, Watanabe K, Kage H, et al. High expression of IRE1 in lung adenocarcinoma is associated with a lower rate of recurrence. Jpn J Clin Oncol. 2017;47:543-550 pubmed publisher
    ..396; 95% confidence interval, 0.188-0.834; P = 0.015). Inositol-requiring kinase 1 may be a useful biomarker to predict recurrence in surgically resected lung adenocarcinoma patients. ..
  85. Wong M, DiChiara A, Suen P, Chen K, Doan N, Shoulders M. Adapting Secretory Proteostasis and Function Through the Unfolded Protein Response. Curr Top Microbiol Immunol. 2018;414:1-25 pubmed publisher
    ..By the action of the transmembrane signal transducers IRE1, PERK, and ATF6, the UPR induces networks of genes whose products alleviate the burden of protein misfolding...
  86. Shen S, Zhou M, Huang K, Wu Y, Ma Y, Wang J, et al. Blocking autophagy enhances the apoptotic effect of 18?-glycyrrhetinic acid on human sarcoma cells via endoplasmic reticulum stress and JNK activation. Cell Death Dis. 2017;8:e3055 pubmed publisher
    ..The present findings showed that GA stimulated autophagy by inducing endoplasmic reticulum (ER) stress via the IRE1-JNK pathway...
  87. Nagai A, Kadowaki H, Maruyama T, Takeda K, Nishitoh H, Ichijo H. USP14 inhibits ER-associated degradation via interaction with IRE1alpha. Biochem Biophys Res Commun. 2009;379:995-1000 pubmed publisher
    ..These findings suggest that USP14 is a novel player in the UPR by serving as a physiological inhibitor of ERAD under the non-stressed condition. ..
  88. Liu G, Guo H, Guo C, Zhao S, Gong D, Zhao Y. Involvement of IRE1? signaling in the hippocampus in patients with mesial temporal lobe epilepsy. Brain Res Bull. 2011;84:94-102 pubmed publisher
    ..We investigated inositol-requiring protein 1? (IRE1?)-mediated ER stress pro-and anti-apoptotic signaling pathways in resected hippocampi from 32 patients with ..
  89. Zeng L, Xiao Q, Chen M, Margariti A, Martin D, Ivetic A, et al. Vascular endothelial cell growth-activated XBP1 splicing in endothelial cells is crucial for angiogenesis. Circulation. 2013;127:1712-22 pubmed publisher
    ..receptor internalization and interaction through C-terminal domain with the unspliced XBP1 and the inositol requiring enzyme 1 ? in the endoplasmic reticulum, leading to inositol requiring enzyme 1 ? phosphorylation and XBP1 mRNA ..
  90. Ma R, Yang L, Niu F, Buch S. HIV Tat-Mediated Induction of Human Brain Microvascular Endothelial Cell Apoptosis Involves Endoplasmic Reticulum Stress and Mitochondrial Dysfunction. Mol Neurobiol. 2016;53:132-142 pubmed publisher
    ..The current study demonstrates that exposure of HBMECs to Tat induces multiple stress responses, including ER stress and mitochondrial dysfunction which in turn lead to apoptosis. ..
  91. Brozzi F, Gerlo S, Grieco F, Juusola M, Balhuizen A, Lievens S, et al. Ubiquitin D Regulates IRE1?/c-Jun N-terminal Kinase (JNK) Protein-dependent Apoptosis in Pancreatic Beta Cells. J Biol Chem. 2016;291:12040-56 pubmed publisher "apoptotic" UPR, but accumulating evidence indicates that signaling by the ER transmembrane protein IRE1? is critical for this transition. IRE1? activation is regulated by both intra-ER and cytosolic cues...
  92. Minchenko D, Riabovol O, Tsymbal D, Ratushna O, Minchenko O. Inhibition of IRE1 signaling affects the expression of genes encoded glucocorticoid receptor and some related factors and their hypoxic regulation in U87 glioma cells. Endocr Regul. 2016;50:127-36 pubmed publisher
    ..was to examine the effect of inhibition of endoplasmic reticulum stress signaling, mediated by IRE1 (inositol requiring enzyme 1), which is a central mediator of the unfolded protein response on the expression of genes encoding ..