The serine/threonine-protein kinase/endoribonuclease inositol-requiring enzyme 1 α (IRE1α) is an enzyme that in humans is encoded by the ERN1gene.[1][2]
The protein encoded by this gene is the ER to nucleus signalling 1 protein, a human homologue of the yeast Ire1 gene product. This protein possesses intrinsic kinase activity and an endoribonuclease activity and it is important in altering gene expression as a response to endoplasmic reticulum-based stress signals (mainly the unfolded protein response). Two alternatively spliced transcript variants encoding different isoforms have been found for this gene.[2]
Signaling
IRE1α possesses two functional enzymatic domains, an endonuclease and a trans-autophosphorylation kinase domain. Upon activation, IRE1α oligomerizes and carries out an unconventional RNA splicing activity, removing an intron from the X-box binding protein 1 (XBP1) mRNA, and allowing it to become translated into a functional transcription factor, XBP1s.[3] XBP1s upregulates ER chaperones and endoplasmic reticulum associated degradation (ERAD) genes that facilitate recovery from ER stress.
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Katayama T, Imaizumi K, Sato N, et al. (2000). "Presenilin-1 mutations downregulate the signalling pathway of the unfolded-protein response". Nat. Cell Biol. 1 (8): 479–85. doi:10.1038/70265. PMID10587643.
Urano F, Wang X, Bertolotti A, et al. (2000). "Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1". Science. 287 (5453): 664–6. doi:10.1126/science.287.5453.664. PMID10650002.
Iwawaki T, Hosoda A, Okuda T, et al. (2001). "Translational control by the ER transmembrane kinase/ribonuclease IRE1 under ER stress". Nat. Cell Biol. 3 (2): 158–64. doi:10.1038/35055065. PMID11175748.
Yoneda T, Imaizumi K, Oono K, et al. (2001). "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. 276 (17): 13935–40. doi:10.1074/jbc.M010677200. PMID11278723.
Liu CY, Wong HN, Schauerte JA, Kaufman RJ (2002). "The protein kinase/endoribonuclease IRE1alpha that signals the unfolded protein response has a luminal N-terminal ligand-independent dimerization domain". J. Biol. Chem. 277 (21): 18346–56. doi:10.1074/jbc.M112454200. PMID11897784.
Liu CY, Xu Z, Kaufman RJ (2003). "Structure and intermolecular interactions of the luminal dimerization domain of human IRE1alpha". J. Biol. Chem. 278 (20): 17680–7. doi:10.1074/jbc.M300418200. PMID12637535.
Kaneko M, Niinuma Y, Nomura Y (2004). "Activation signal of nuclear factor-kappa B in response to endoplasmic reticulum stress is transduced via IRE1 and tumor necrosis factor receptor-associated factor 2". Biol. Pharm. Bull. 26 (7): 931–5. doi:10.1248/bpb.26.931. PMID12843613.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID14702039.
Shang J, Lehrman MA (2004). "Discordance of UPR signaling by ATF6 and Ire1p-XBP1 with levels of target transcripts". Biochem. Biophys. Res. Commun. 317 (2): 390–6. doi:10.1016/j.bbrc.2004.03.058. PMID15063770.
Oono K, Yoneda T, Manabe T, et al. (2004). "JAB1 participates in unfolded protein responses by association and dissociation with IRE1". Neurochem. Int. 45 (5): 765–72. doi:10.1016/j.neuint.2004.01.003. PMID15234121.
Hetz C, Bernasconi P, Fisher J, et al. (2006). "Proapoptotic BAX and BAK modulate the unfolded protein response by a direct interaction with IRE1alpha". Science. 312 (5773): 572–6. doi:10.1126/science.1123480. PMID16645094.
Oikawa D, Tokuda M, Iwawaki T (2007). "Site-specific cleavage of CD59 mRNA by endoplasmic reticulum-localized ribonuclease, IRE1". Biochem. Biophys. Res. Commun. 360 (1): 122–7. doi:10.1016/j.bbrc.2007.06.020. PMID17585877.