Gene Symbol: ire-1
Description: IRE1 kinase related;Serine/threonine-protein kinase
Alias: IRE1 kinase related;Serine/threonine-protein kinase
Species: Caenorhabditis elegans

Top Publications

  1. Calfon M, Zeng H, Urano F, Till J, Hubbard S, Harding H, et al. IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA. Nature. 2002;415:92-6 pubmed
    ..Our findings suggest that physiological ER load regulates a developmental decision in higher eukaryotes. ..
  2. Shen X, Ellis R, Sakaki K, Kaufman R. Genetic interactions due to constitutive and inducible gene regulation mediated by the unfolded protein response in C. elegans. PLoS Genet. 2005;1:e37 pubmed
    ..Finally, our array study identified the liver-specific transcription factor CREBh as a novel UPR gene conserved during metazoan evolution. ..
  3. Richardson C, Kinkel S, Kim D. Physiological IRE-1-XBP-1 and PEK-1 signaling in Caenorhabditis elegans larval development and immunity. PLoS Genet. 2011;7:e1002391 pubmed publisher
  4. 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. ..
  5. Safra M, Ben Hamo S, Kenyon C, Henis Korenblit S. The ire-1 ER stress-response pathway is required for normal secretory-protein metabolism in C. elegans. J Cell Sci. 2013;126:4136-46 pubmed publisher
    ..elegans model of Alzheimer's disease. Taken together, our findings indicate that UPR genes are critical for maintaining secretory protein metabolism under normal growth conditions. ..
  6. Salzberg Y, Coleman A, Celestrin K, Cohen Berkman M, Biederer T, Henis Korenblit S, et al. Reduced Insulin/Insulin-Like Growth Factor Receptor Signaling Mitigates Defective Dendrite Morphogenesis in Mutants of the ER Stress Sensor IRE-1. PLoS Genet. 2017;13:e1006579 pubmed publisher
  7. Kapulkin W, Kapulkin V, Hiester B, Link C. Compensatory regulation among ER chaperones in C. elegans. FEBS Lett. 2005;579:3063-8 pubmed
    ..We show that this compensatory regulation is specific for ER chaperones, not dependent on RNA interference, and required for maintaining viability in worms containing a deletion of the hsp-3 gene. ..
  8. Uccelletti D, Pascoli A, Farina F, Alberti A, Mancini P, Hirschberg C, et al. APY-1, a novel Caenorhabditis elegans apyrase involved in unfolded protein response signalling and stress responses. Mol Biol Cell. 2008;19:1337-45 pubmed publisher
  9. Chen D, Thomas E, Kapahi P. HIF-1 modulates dietary restriction-mediated lifespan extension via IRE-1 in Caenorhabditis elegans. PLoS Genet. 2009;5:e1000486 pubmed publisher
    ..Therefore, our results demonstrate a tissue-specific role for HIF-1 in the lifespan extension by DR involving the IRE-1 ER stress pathway. ..

More Information


  1. Eisermann D, Wenzel U, Fitzenberger E. PEK-1 is crucial for hormesis induced by inhibition of the IRE-1/XBP-1 pathway in the Caenorhabditis elegans mev-1 mutant. Biochem Biophys Res Commun. 2016;473:1052-1057 pubmed publisher
    ..In conclusion, we identified PEK-1 as a mediator of hormesis in the mev-1 mutant of C. elegans which is induced by simultaneous inhibition of XBP-1 and its splicing activator IRE-1 and mediated through activation of the proteasome. ..
  2. Mao X, Crowder C. Protein misfolding induces hypoxic preconditioning via a subset of the unfolded protein response machinery. Mol Cell Biol. 2010;30:5033-42 pubmed publisher
    ..These data suggest a model where hypoxia-induced misfolded proteins trigger the activation of IRE-1, which along with GCN-2 controls an adaptive response that is essential to HP. ..
  3. Bischof L, Kao C, Los F, Gonzalez M, Shen Z, Briggs S, et al. Activation of the unfolded protein response is required for defenses against bacterial pore-forming toxin in vivo. PLoS Pathog. 2008;4:e1000176 pubmed publisher
    ..These data demonstrate that the UPR, a fundamental intracellular pathway, can operate in intrinsic cellular defenses against bacterial attack. ..
  4. Eletto D, Eletto D, Dersh D, Gidalevitz T, Argon Y. Protein disulfide isomerase A6 controls the decay of IRE1? signaling via disulfide-dependent association. Mol Cell. 2014;53:562-576 pubmed publisher
    ..Thus, PDIA6 activity provides a mechanism that limits UPR signaling and maintains it within a physiologically appropriate range...
  5. Jo H, Shim J, Lee J, Lee J, Kim J. IRE-1 and HSP-4 contribute to energy homeostasis via fasting-induced lipases in C. elegans. Cell Metab. 2009;9:440-8 pubmed publisher
    ..These data suggest that the ER-resident proteins IRE-1 and HSP-4 are key nutritional sensors that modulate expression of inducible lipases to maintain whole-body energy homeostasis in C. elegans. ..
  6. Mark K, Dumas K, Bhaumik D, Schilling B, Davis S, Oron T, et al. Vitamin D Promotes Protein Homeostasis and Longevity via the Stress Response Pathway Genes skn-1, ire-1, and xbp-1. Cell Rep. 2016;17:1227-1237 pubmed publisher
  7. Levi Ferber M, Gian H, Dudkevich R, Henis Korenblit S. Transdifferentiation mediated tumor suppression by the endoplasmic reticulum stress sensor IRE-1 in C. elegans. elife. 2015;4: pubmed publisher
    ..Our results indicate that tumor cell transdifferentiation has the potential to combat cancer and overcome the escape of tumor cells from the cell death machinery. ..
  8. Levi Ferber M, Salzberg Y, Safra M, Haviv Chesner A, Bülow H, Henis Korenblit S. It's all in your mind: determining germ cell fate by neuronal IRE-1 in C. elegans. PLoS Genet. 2014;10:e1004747 pubmed publisher
    ..Altogether, our findings uncover ire-1 as a novel cell non-autonomous regulator of germ cell apoptosis, linking ER homeostasis in sensory neurons and germ cell fate. ..
  9. Schipanski A, Lange S, Segref A, Gutschmidt A, Lomas D, Miranda E, et al. A novel interaction between aging and ER overload in a protein conformational dementia. Genetics. 2013;193:865-76 pubmed publisher
    ..These data suggest that targets aimed at increasing UPR capacity in neurons are valuable tools for therapeutic intervention. ..
  10. Henis Korenblit S, Zhang P, Hansen M, McCormick M, Lee S, Cary M, et al. Insulin/IGF-1 signaling mutants reprogram ER stress response regulators to promote longevity. Proc Natl Acad Sci U S A. 2010;107:9730-5 pubmed publisher
    ..Instead, in insulin/IGF-1 pathway mutants, XBP-1 collaborates with DAF-16, a FOXO-transcription factor that is activated in these mutants, to enhance ER stress resistance and to activate new genes that promote longevity. ..
  11. Hourihan J, Moronetti Mazzeo L, Fernández Cárdenas L, Blackwell T. Cysteine Sulfenylation Directs IRE-1 to Activate the SKN-1/Nrf2 Antioxidant Response. Mol Cell. 2016;63:553-566 pubmed publisher
  12. Anderson L, Mao X, Scott B, Crowder C. Survival from hypoxia in C. elegans by inactivation of aminoacyl-tRNA synthetases. Science. 2009;323:630-3 pubmed publisher
    ..Thus, translational suppression produces hypoxia resistance, in part by reducing unfolded protein toxicity. ..
  13. Lee D, Singaravelu G, Park B, Ahnn J. Differential requirement of unfolded protein response pathway for calreticulin expression in Caenorhabditis elegans. J Mol Biol. 2007;372:331-40 pubmed
  14. Safra M, Fickentscher R, Levi Ferber M, Danino Y, Haviv Chesner A, Hansen M, et al. The FOXO transcription factor DAF-16 bypasses ire-1 requirement to promote endoplasmic reticulum homeostasis. Cell Metab. 2014;20:870-81 pubmed
    ..Because there is no sensor in the ER that activates DAF-16 in response to intrinsic ER stress, natural or artificial interventions that activate DAF-16 may be useful therapeutic approaches to maintain ER homeostasis. ..
  15. Mathew R, Pal Bhadra M, Bhadra U. Insulin/insulin-like growth factor-1 signalling (IIS) based regulation of lifespan across species. Biogerontology. 2017;18:35-53 pubmed publisher
    ..Enhanced study of the role of IIS pathway and epigenetic mechanisms that regulate aging may facilitate progressive prevention and treatment of human age-related diseases. ..