The serine/threonine-protein kinase/endoribonuclease inositol-requiring enzyme 1 α (IRE1α) is an enzyme that in humans is encoded by the ERN1 gene. [5] [6]
Function
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. [6]
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. [7] XBP1s upregulates ER chaperones and endoplasmic reticulum associated degradation ( ERAD) genes that facilitate recovery from ER stress.
Clinical significance
As IRE1α is a primary sensor for unfolded protein response, its disruption could be linked with neurodegenerative diseases, by which the accumulation of intracellular toxic proteins serves as one of the key pathogenic mechanisms. [8] IRE1 signalling is considered to be pathogenic in Alzheimer's disease, [9] Parkinson's disease [10] and amyotrophic lateral sclerosis. [11] [12]
Interactions
ERN1 has been shown to interact with Heat shock protein 90kDa alpha (cytosolic), member A1. [13]
Inhibitors
Two types of inhibitors exist targeting either the catalytic core of the RNase domain or the ATP-binding pocket of the kinase domain.
RNase domain inhibitors
Salicylaldehydes (3-methoxy-6-bromosalicylaldehyde, [14] 4μ8C, [15] MKC-3946, [16] STF-083010, [17] toyocamycin. [18]
ATP-binding pocket
Sunitinib and APY29 inhibit the ATP-binding pocket but allosterically activate the IRE1α RNase domain.
Compound 3 prevents kinase activity, oligomerization and RNase activity. [19]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000178607 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000020715 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Tirasophon W, Welihinda AA, Kaufman RJ (June 1998). "A stress response pathway from the endoplasmic reticulum to the nucleus requires a novel bifunctional protein kinase/endoribonuclease (Ire1p) in mammalian cells". Genes & Development. 12 (12): 1812–1824. doi: 10.1101/gad.12.12.1812. PMC 316900. PMID 9637683.
- ^ a b "Entrez Gene: ERN1 endoplasmic reticulum to nucleus signalling 1".
- ^ Calfon M, Zeng H, Urano F, Till JH, Hubbard SR, Harding HP, et al. (January 2002). "IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA". Nature. 415 (6867): 92–96. Bibcode: 2002Natur.415...92C. doi: 10.1038/415092a. PMID 11780124. S2CID 4319118.
- ^ Kurtishi A, Rosen B, Patil KS, Alves GW, Møller SG (May 2019). "Cellular Proteostasis in Neurodegeneration". Molecular Neurobiology. 56 (5): 3676–3689. doi: 10.1007/s12035-018-1334-z. PMID 30182337. S2CID 52158118.
- ^ Duran-Aniotz C, Cornejo VH, Espinoza S, Ardiles ÁO, Medinas DB, Salazar C, et al. (September 2017). "IRE1 signaling exacerbates Alzheimer's disease pathogenesis". Acta Neuropathologica. 134 (3): 489–506. doi: 10.1007/s00401-017-1694-x. PMID 28341998. S2CID 9380354.
- ^ Yan C, Liu J, Gao J, Sun Y, Zhang L, Song H, et al. (October 2019). "IRE1 promotes neurodegeneration through autophagy-dependent neuron death in the Drosophila model of Parkinson's disease". Cell Death & Disease. 10 (11): 800. doi: 10.1038/s41419-019-2039-6. PMC 6805898. PMID 31641108.
- ^ Montibeller L, de Belleroche J (September 2018). "Amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD) are characterised by differential activation of ER stress pathways: focus on UPR target genes". Cell Stress & Chaperones. 23 (5): 897–912. doi: 10.1007/s12192-018-0897-y. PMC 6111088. PMID 29725981.
- ^ Chen D, Wang Y, Chin ER (2015-05-18). "Activation of the endoplasmic reticulum stress response in skeletal muscle of G93A*SOD1 amyotrophic lateral sclerosis mice". Frontiers in Cellular Neuroscience. 9: 170. doi: 10.3389/fncel.2015.00170. PMC 4435075. PMID 26041991.
- ^ Marcu MG, Doyle M, Bertolotti A, Ron D, Hendershot L, Neckers L (December 2002). "Heat shock protein 90 modulates the unfolded protein response by stabilizing IRE1alpha". Molecular and Cellular Biology. 22 (24): 8506–8513. doi: 10.1128/MCB.22.24.8506-8513.2002. PMC 139892. PMID 12446770.
- ^ Volkmann K, Lucas JL, Vuga D, Wang X, Brumm D, Stiles C, et al. (April 2011). "Potent and selective inhibitors of the inositol-requiring enzyme 1 endoribonuclease". The Journal of Biological Chemistry. 286 (14): 12743–12755. doi: 10.1074/jbc.M110.199737. PMC 3069474. PMID 21303903.
- ^ Cross BC, Bond PJ, Sadowski PG, Jha BK, Zak J, Goodman JM, et al. (April 2012). "The molecular basis for selective inhibition of unconventional mRNA splicing by an IRE1-binding small molecule". Proceedings of the National Academy of Sciences of the United States of America. 109 (15): E869–E878. doi: 10.1073/pnas.1115623109. PMC 3326519. PMID 22315414.
- ^ Mimura N, Fulciniti M, Gorgun G, Tai YT, Cirstea D, Santo L, et al. (June 2012). "Blockade of XBP1 splicing by inhibition of IRE1α is a promising therapeutic option in multiple myeloma". Blood. 119 (24): 5772–5781. doi: 10.1182/blood-2011-07-366633. PMC 3382937. PMID 22538852.
- ^ Papandreou I, Denko NC, Olson M, Van Melckebeke H, Lust S, Tam A, et al. (January 2011). "Identification of an Ire1alpha endonuclease specific inhibitor with cytotoxic activity against human multiple myeloma". Blood. 117 (4): 1311–1314. doi: 10.1182/blood-2010-08-303099. PMC 3056474. PMID 21081713.
- ^ Ri M, Tashiro E, Oikawa D, Shinjo S, Tokuda M, Yokouchi Y, et al. (July 2012). "Identification of Toyocamycin, an agent cytotoxic for multiple myeloma cells, as a potent inhibitor of ER stress-induced XBP1 mRNA splicing". Blood Cancer Journal. 2 (7): e79. doi: 10.1038/bcj.2012.26. PMC 3408640. PMID 22852048.
- ^ Wang L, Perera BG, Hari SB, Bhhatarai B, Backes BJ, Seeliger MA, et al. (December 2012). "Divergent allosteric control of the IRE1α endoribonuclease using kinase inhibitors". Nature Chemical Biology. 8 (12): 982–989. doi: 10.1038/nchembio.1094. PMC 3508346. PMID 23086298.
Further reading
- Katayama T, Imaizumi K, Sato N, Miyoshi K, Kudo T, Hitomi J, et al. (December 1999). "Presenilin-1 mutations downregulate the signalling pathway of the unfolded-protein response". Nature Cell Biology. 1 (8): 479–485. doi: 10.1038/70265. PMID 10587643. S2CID 30259483.
- Urano F, Wang X, Bertolotti A, Zhang Y, Chung P, Harding HP, Ron D (January 2000). "Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1". Science. 287 (5453): 664–666. Bibcode: 2000Sci...287..664U. doi: 10.1126/science.287.5453.664. PMID 10650002. S2CID 9154084.
- Dias Neto E, Correa RG, Verjovski-Almeida S, Briones MR, Nagai MA, da Silva W, et al. (March 2000). "Shotgun sequencing of the human transcriptome with ORF expressed sequence tags". Proceedings of the National Academy of Sciences of the United States of America. 97 (7): 3491–3496. Bibcode: 2000PNAS...97.3491D. doi: 10.1073/pnas.97.7.3491. PMC 16267. PMID 10737800.
- Iwawaki T, Hosoda A, Okuda T, Kamigori Y, Nomura-Furuwatari C, Kimata Y, et al. (February 2001). "Translational control by the ER transmembrane kinase/ribonuclease IRE1 under ER stress". Nature Cell Biology. 3 (2): 158–164. doi: 10.1038/35055065. PMID 11175748. S2CID 7756732.
- Yoneda T, Imaizumi K, Oono K, Yui D, Gomi F, Katayama T, Tohyama M (April 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". The Journal of Biological Chemistry. 276 (17): 13935–13940. doi: 10.1074/jbc.M010677200. PMID 11278723.
- Lee K, Tirasophon W, Shen X, Michalak M, Prywes R, Okada T, et al. (February 2002). "IRE1-mediated unconventional mRNA splicing and S2P-mediated ATF6 cleavage merge to regulate XBP1 in signaling the unfolded protein response". Genes & Development. 16 (4): 452–466. doi: 10.1101/gad.964702. PMC 155339. PMID 11850408.
- Liu CY, Wong HN, Schauerte JA, Kaufman RJ (May 2002). "The protein kinase/endoribonuclease IRE1alpha that signals the unfolded protein response has a luminal N-terminal ligand-independent dimerization domain". The Journal of Biological Chemistry. 277 (21): 18346–18356. doi: 10.1074/jbc.M112454200. PMID 11897784.
- Nishitoh H, Matsuzawa A, Tobiume K, Saegusa K, Takeda K, Inoue K, et al. (June 2002). "ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death triggered by expanded polyglutamine repeats". Genes & Development. 16 (11): 1345–1355. doi: 10.1101/gad.992302. PMC 186318. PMID 12050113.
- Marcu MG, Doyle M, Bertolotti A, Ron D, Hendershot L, Neckers L (December 2002). "Heat shock protein 90 modulates the unfolded protein response by stabilizing IRE1alpha". Molecular and Cellular Biology. 22 (24): 8506–8513. doi: 10.1128/MCB.22.24.8506-8513.2002. PMC 139892. PMID 12446770.
- Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, et al. (December 2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proceedings of the National Academy of Sciences of the United States of America. 99 (26): 16899–16903. Bibcode: 2002PNAS...9916899M. doi: 10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Liu CY, Xu Z, Kaufman RJ (May 2003). "Structure and intermolecular interactions of the luminal dimerization domain of human IRE1alpha". The Journal of Biological Chemistry. 278 (20): 17680–17687. doi: 10.1074/jbc.M300418200. PMID 12637535.
- Kaneko M, Niinuma Y, Nomura Y (July 2003). "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". Biological & Pharmaceutical Bulletin. 26 (7): 931–935. doi: 10.1248/bpb.26.931. PMID 12843613.
- Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, et al. (January 2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nature Genetics. 36 (1): 40–45. doi: 10.1038/ng1285. PMID 14702039.
- Shang J, Lehrman MA (April 2004). "Discordance of UPR signaling by ATF6 and Ire1p-XBP1 with levels of target transcripts". Biochemical and Biophysical Research Communications. 317 (2): 390–396. doi: 10.1016/j.bbrc.2004.03.058. PMID 15063770.
- Oono K, Yoneda T, Manabe T, Yamagishi S, Matsuda S, Hitomi J, et al. (October 2004). "JAB1 participates in unfolded protein responses by association and dissociation with IRE1". Neurochemistry International. 45 (5): 765–772. doi: 10.1016/j.neuint.2004.01.003. PMID 15234121. S2CID 11627892.
- Huang ZM, Tan T, Yoshida H, Mori K, Ma Y, Yen TS (September 2005). "Activation of hepatitis B virus S promoter by a cell type-restricted IRE1-dependent pathway induced by endoplasmic reticulum stress". Molecular and Cellular Biology. 25 (17): 7522–7533. doi: 10.1128/MCB.25.17.7522-7533.2005. PMC 1190304. PMID 16107700.
- Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, et al. (January 2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Research. 16 (1): 55–65. doi: 10.1101/gr.4039406. PMC 1356129. PMID 16344560.
- Hetz C, Bernasconi P, Fisher J, Lee AH, Bassik MC, Antonsson B, et al. (April 2006). "Proapoptotic BAX and BAK modulate the unfolded protein response by a direct interaction with IRE1alpha". Science. 312 (5773): 572–576. Bibcode: 2006Sci...312..572H. doi: 10.1126/science.1123480. PMID 16645094. S2CID 9135901.
- Oikawa D, Tokuda M, Iwawaki T (August 2007). "Site-specific cleavage of CD59 mRNA by endoplasmic reticulum-localized ribonuclease, IRE1". Biochemical and Biophysical Research Communications. 360 (1): 122–127. doi: 10.1016/j.bbrc.2007.06.020. PMID 17585877.
PDB gallery | |
|---|---|
|
| ERN1 | |||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | ERN1, IRE1, IRE1P, IRE1a, hIRE1p, endoplasmic reticulum to nucleus signaling 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 604033; MGI: 1930134; HomoloGene: 55580; GeneCards: ERN1; OMA: ERN1 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
The serine/threonine-protein kinase/endoribonuclease inositol-requiring enzyme 1 α (IRE1α) is an enzyme that in humans is encoded by the ERN1 gene. [5] [6]
Function
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. [6]
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. [7] XBP1s upregulates ER chaperones and endoplasmic reticulum associated degradation ( ERAD) genes that facilitate recovery from ER stress.
Clinical significance
As IRE1α is a primary sensor for unfolded protein response, its disruption could be linked with neurodegenerative diseases, by which the accumulation of intracellular toxic proteins serves as one of the key pathogenic mechanisms. [8] IRE1 signalling is considered to be pathogenic in Alzheimer's disease, [9] Parkinson's disease [10] and amyotrophic lateral sclerosis. [11] [12]
Interactions
ERN1 has been shown to interact with Heat shock protein 90kDa alpha (cytosolic), member A1. [13]
Inhibitors
Two types of inhibitors exist targeting either the catalytic core of the RNase domain or the ATP-binding pocket of the kinase domain.
RNase domain inhibitors
Salicylaldehydes (3-methoxy-6-bromosalicylaldehyde, [14] 4μ8C, [15] MKC-3946, [16] STF-083010, [17] toyocamycin. [18]
ATP-binding pocket
Sunitinib and APY29 inhibit the ATP-binding pocket but allosterically activate the IRE1α RNase domain.
Compound 3 prevents kinase activity, oligomerization and RNase activity. [19]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000178607 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000020715 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Tirasophon W, Welihinda AA, Kaufman RJ (June 1998). "A stress response pathway from the endoplasmic reticulum to the nucleus requires a novel bifunctional protein kinase/endoribonuclease (Ire1p) in mammalian cells". Genes & Development. 12 (12): 1812–1824. doi: 10.1101/gad.12.12.1812. PMC 316900. PMID 9637683.
- ^ a b "Entrez Gene: ERN1 endoplasmic reticulum to nucleus signalling 1".
- ^ Calfon M, Zeng H, Urano F, Till JH, Hubbard SR, Harding HP, et al. (January 2002). "IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA". Nature. 415 (6867): 92–96. Bibcode: 2002Natur.415...92C. doi: 10.1038/415092a. PMID 11780124. S2CID 4319118.
- ^ Kurtishi A, Rosen B, Patil KS, Alves GW, Møller SG (May 2019). "Cellular Proteostasis in Neurodegeneration". Molecular Neurobiology. 56 (5): 3676–3689. doi: 10.1007/s12035-018-1334-z. PMID 30182337. S2CID 52158118.
- ^ Duran-Aniotz C, Cornejo VH, Espinoza S, Ardiles ÁO, Medinas DB, Salazar C, et al. (September 2017). "IRE1 signaling exacerbates Alzheimer's disease pathogenesis". Acta Neuropathologica. 134 (3): 489–506. doi: 10.1007/s00401-017-1694-x. PMID 28341998. S2CID 9380354.
- ^ Yan C, Liu J, Gao J, Sun Y, Zhang L, Song H, et al. (October 2019). "IRE1 promotes neurodegeneration through autophagy-dependent neuron death in the Drosophila model of Parkinson's disease". Cell Death & Disease. 10 (11): 800. doi: 10.1038/s41419-019-2039-6. PMC 6805898. PMID 31641108.
- ^ Montibeller L, de Belleroche J (September 2018). "Amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD) are characterised by differential activation of ER stress pathways: focus on UPR target genes". Cell Stress & Chaperones. 23 (5): 897–912. doi: 10.1007/s12192-018-0897-y. PMC 6111088. PMID 29725981.
- ^ Chen D, Wang Y, Chin ER (2015-05-18). "Activation of the endoplasmic reticulum stress response in skeletal muscle of G93A*SOD1 amyotrophic lateral sclerosis mice". Frontiers in Cellular Neuroscience. 9: 170. doi: 10.3389/fncel.2015.00170. PMC 4435075. PMID 26041991.
- ^ Marcu MG, Doyle M, Bertolotti A, Ron D, Hendershot L, Neckers L (December 2002). "Heat shock protein 90 modulates the unfolded protein response by stabilizing IRE1alpha". Molecular and Cellular Biology. 22 (24): 8506–8513. doi: 10.1128/MCB.22.24.8506-8513.2002. PMC 139892. PMID 12446770.
- ^ Volkmann K, Lucas JL, Vuga D, Wang X, Brumm D, Stiles C, et al. (April 2011). "Potent and selective inhibitors of the inositol-requiring enzyme 1 endoribonuclease". The Journal of Biological Chemistry. 286 (14): 12743–12755. doi: 10.1074/jbc.M110.199737. PMC 3069474. PMID 21303903.
- ^ Cross BC, Bond PJ, Sadowski PG, Jha BK, Zak J, Goodman JM, et al. (April 2012). "The molecular basis for selective inhibition of unconventional mRNA splicing by an IRE1-binding small molecule". Proceedings of the National Academy of Sciences of the United States of America. 109 (15): E869–E878. doi: 10.1073/pnas.1115623109. PMC 3326519. PMID 22315414.
- ^ Mimura N, Fulciniti M, Gorgun G, Tai YT, Cirstea D, Santo L, et al. (June 2012). "Blockade of XBP1 splicing by inhibition of IRE1α is a promising therapeutic option in multiple myeloma". Blood. 119 (24): 5772–5781. doi: 10.1182/blood-2011-07-366633. PMC 3382937. PMID 22538852.
- ^ Papandreou I, Denko NC, Olson M, Van Melckebeke H, Lust S, Tam A, et al. (January 2011). "Identification of an Ire1alpha endonuclease specific inhibitor with cytotoxic activity against human multiple myeloma". Blood. 117 (4): 1311–1314. doi: 10.1182/blood-2010-08-303099. PMC 3056474. PMID 21081713.
- ^ Ri M, Tashiro E, Oikawa D, Shinjo S, Tokuda M, Yokouchi Y, et al. (July 2012). "Identification of Toyocamycin, an agent cytotoxic for multiple myeloma cells, as a potent inhibitor of ER stress-induced XBP1 mRNA splicing". Blood Cancer Journal. 2 (7): e79. doi: 10.1038/bcj.2012.26. PMC 3408640. PMID 22852048.
- ^ Wang L, Perera BG, Hari SB, Bhhatarai B, Backes BJ, Seeliger MA, et al. (December 2012). "Divergent allosteric control of the IRE1α endoribonuclease using kinase inhibitors". Nature Chemical Biology. 8 (12): 982–989. doi: 10.1038/nchembio.1094. PMC 3508346. PMID 23086298.
Further reading
- Katayama T, Imaizumi K, Sato N, Miyoshi K, Kudo T, Hitomi J, et al. (December 1999). "Presenilin-1 mutations downregulate the signalling pathway of the unfolded-protein response". Nature Cell Biology. 1 (8): 479–485. doi: 10.1038/70265. PMID 10587643. S2CID 30259483.
- Urano F, Wang X, Bertolotti A, Zhang Y, Chung P, Harding HP, Ron D (January 2000). "Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1". Science. 287 (5453): 664–666. Bibcode: 2000Sci...287..664U. doi: 10.1126/science.287.5453.664. PMID 10650002. S2CID 9154084.
- Dias Neto E, Correa RG, Verjovski-Almeida S, Briones MR, Nagai MA, da Silva W, et al. (March 2000). "Shotgun sequencing of the human transcriptome with ORF expressed sequence tags". Proceedings of the National Academy of Sciences of the United States of America. 97 (7): 3491–3496. Bibcode: 2000PNAS...97.3491D. doi: 10.1073/pnas.97.7.3491. PMC 16267. PMID 10737800.
- Iwawaki T, Hosoda A, Okuda T, Kamigori Y, Nomura-Furuwatari C, Kimata Y, et al. (February 2001). "Translational control by the ER transmembrane kinase/ribonuclease IRE1 under ER stress". Nature Cell Biology. 3 (2): 158–164. doi: 10.1038/35055065. PMID 11175748. S2CID 7756732.
- Yoneda T, Imaizumi K, Oono K, Yui D, Gomi F, Katayama T, Tohyama M (April 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". The Journal of Biological Chemistry. 276 (17): 13935–13940. doi: 10.1074/jbc.M010677200. PMID 11278723.
- Lee K, Tirasophon W, Shen X, Michalak M, Prywes R, Okada T, et al. (February 2002). "IRE1-mediated unconventional mRNA splicing and S2P-mediated ATF6 cleavage merge to regulate XBP1 in signaling the unfolded protein response". Genes & Development. 16 (4): 452–466. doi: 10.1101/gad.964702. PMC 155339. PMID 11850408.
- Liu CY, Wong HN, Schauerte JA, Kaufman RJ (May 2002). "The protein kinase/endoribonuclease IRE1alpha that signals the unfolded protein response has a luminal N-terminal ligand-independent dimerization domain". The Journal of Biological Chemistry. 277 (21): 18346–18356. doi: 10.1074/jbc.M112454200. PMID 11897784.
- Nishitoh H, Matsuzawa A, Tobiume K, Saegusa K, Takeda K, Inoue K, et al. (June 2002). "ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death triggered by expanded polyglutamine repeats". Genes & Development. 16 (11): 1345–1355. doi: 10.1101/gad.992302. PMC 186318. PMID 12050113.
- Marcu MG, Doyle M, Bertolotti A, Ron D, Hendershot L, Neckers L (December 2002). "Heat shock protein 90 modulates the unfolded protein response by stabilizing IRE1alpha". Molecular and Cellular Biology. 22 (24): 8506–8513. doi: 10.1128/MCB.22.24.8506-8513.2002. PMC 139892. PMID 12446770.
- Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, et al. (December 2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proceedings of the National Academy of Sciences of the United States of America. 99 (26): 16899–16903. Bibcode: 2002PNAS...9916899M. doi: 10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Liu CY, Xu Z, Kaufman RJ (May 2003). "Structure and intermolecular interactions of the luminal dimerization domain of human IRE1alpha". The Journal of Biological Chemistry. 278 (20): 17680–17687. doi: 10.1074/jbc.M300418200. PMID 12637535.
- Kaneko M, Niinuma Y, Nomura Y (July 2003). "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". Biological & Pharmaceutical Bulletin. 26 (7): 931–935. doi: 10.1248/bpb.26.931. PMID 12843613.
- Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, et al. (January 2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nature Genetics. 36 (1): 40–45. doi: 10.1038/ng1285. PMID 14702039.
- Shang J, Lehrman MA (April 2004). "Discordance of UPR signaling by ATF6 and Ire1p-XBP1 with levels of target transcripts". Biochemical and Biophysical Research Communications. 317 (2): 390–396. doi: 10.1016/j.bbrc.2004.03.058. PMID 15063770.
- Oono K, Yoneda T, Manabe T, Yamagishi S, Matsuda S, Hitomi J, et al. (October 2004). "JAB1 participates in unfolded protein responses by association and dissociation with IRE1". Neurochemistry International. 45 (5): 765–772. doi: 10.1016/j.neuint.2004.01.003. PMID 15234121. S2CID 11627892.
- Huang ZM, Tan T, Yoshida H, Mori K, Ma Y, Yen TS (September 2005). "Activation of hepatitis B virus S promoter by a cell type-restricted IRE1-dependent pathway induced by endoplasmic reticulum stress". Molecular and Cellular Biology. 25 (17): 7522–7533. doi: 10.1128/MCB.25.17.7522-7533.2005. PMC 1190304. PMID 16107700.
- Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, et al. (January 2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Research. 16 (1): 55–65. doi: 10.1101/gr.4039406. PMC 1356129. PMID 16344560.
- Hetz C, Bernasconi P, Fisher J, Lee AH, Bassik MC, Antonsson B, et al. (April 2006). "Proapoptotic BAX and BAK modulate the unfolded protein response by a direct interaction with IRE1alpha". Science. 312 (5773): 572–576. Bibcode: 2006Sci...312..572H. doi: 10.1126/science.1123480. PMID 16645094. S2CID 9135901.
- Oikawa D, Tokuda M, Iwawaki T (August 2007). "Site-specific cleavage of CD59 mRNA by endoplasmic reticulum-localized ribonuclease, IRE1". Biochemical and Biophysical Research Communications. 360 (1): 122–127. doi: 10.1016/j.bbrc.2007.06.020. PMID 17585877.
PDB gallery | |
|---|---|
|