The DOI matches its Crossref record; 19 of the 19 references it cites were found in a registry or an index.
The Unfolded Protein Response: Integrating Stress Signals Through the Stress Sensor IRE1α
Open accessAbstract
Stress induced by accumulation of unfolded proteins at the endoplasmic reticulum (ER) is a classic feature of secretory cells and is observed in many tissues in human diseases including cancer, diabetes, obesity, and neurodegeneration. Cellular adaptation to ER stress is achieved by the activation of the unfolded protein response (UPR), an integrated signal transduction pathway that transmits information about the protein folding status at the ER to the nucleus and cytosol to restore ER homeostasis. Inositol-requiring transmembrane kinase/endonuclease-1 (IRE1α), the most conserved UPR stress sensor, functions as an endoribonuclease that processes the mRNA of the transcription factor X-box binding protein-1 (XBP1). IRE1α signaling is a highly regulated process, controlled by the formation of a dynamic scaffold onto which many regulatory components assemble, here referred to as the UPRosome. Here we provide an overview of the signaling and regulatory mechanisms underlying IRE1α function and discuss the emerging role of the UPR in adaptation to protein folding stress in specialized secretory cells and in pathological conditions associated with alterations in ER homeostasis.
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Citations
Cites
Autophagy fights disease through cellular self-digestion
Mizushima, N., Levine, B., Cuervo, A. M., & Klionsky, D. J. (2008) · Nature · doi:10.1038/nature06639 · Cited by 6,452
Danial, N. N., & Korsmeyer, S. J. (2004) · Cell · doi:10.1016/s0092-8674(04)00046-7 · Cited by 4,651
Endoplasmic Reticulum Stress Links Obesity, Insulin Action, and Type 2 Diabetes
Özcan, U., Cao, Q., Yilmaz, E., Lee, A.-H., Iwakoshi, N. N., Özdelen, E., Tuncman, G., Görgün, C., Glimcher, L. H., & Hotamisligil, G. S. (2004) · Science · doi:10.1126/science.1103160 · Cited by 3,844
Self-citationRegulation mechanisms and signaling pathways of autophagy
He, C., & Klionsky, D. J. (2009) · Annual Review of Genetics · doi:10.1146/annurev-genet-102808-114910 · Cited by 3,609
Autophagy and the Integrated Stress Response
Kroemer, G., Mariño, G., & Levine, B. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.09.023 · Cited by 3,506
One step at a time: endoplasmic reticulum-associated degradation
Vembar, S. S., & Brodsky, J. L. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2546 · Cited by 1,299
TLR activation of the transcription factor XBP1 regulates innate immune responses in macrophages
Martinon, F., Chen, X., Lee, A.-H., & Glimcher, L. H. (2010) · Nature Immunology · doi:10.1038/ni.1857 · Cited by 996 · cited 6×
“IRE1 activation by TLR engagement does not induce ER stress target genes, but is required for optimal and sustained production of proinflammatory cytokines in macrophages (112).”
BackgroundResultInfluentialSelf-citationProtein translocation across the eukaryotic endoplasmic reticulum and bacterial plasma membranes.
Rapoport, T. A. (2007) · Nature · doi:10.1038/nature06384 · Cited by 977
Yoshida, H., Okada, T., Haze, K., Yanagi, H., Yura, T., Negishi, M., & Mori, K. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.18.6755-6767.2000 · Cited by 934
ER stress and neurodegenerative diseases
Lindholm, D., Wootz, H., & Korhonen, L. (2006) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4401778 · Cited by 882
Delépine, M., Nicolino, M., Barrett, T., Golamaully, M., Mark Lathrop, G., & Julier, C. (2000) · Nature Genetics · doi:10.1038/78085 · Cited by 813
The unfolded protein response signals through high-order assembly of Ire1
Korennykh, A. V., Egea, P. F., Korostelev, A. A., Finer-Moore, J., Zhang, C., Shokat, K. M., Stroud, R. M., & Walter, P. (2009) · Nature · doi:10.1038/nature07661 · Cited by 656
Sriburi, R., Jackowski, S., Mori, K., & Brewer, J. W. (2004) · The Journal of Cell Biology · doi:10.1083/jcb.200406136 · Cited by 653
Hetz, C., Thielen, P., Matus, S., Nassif, M., Court, F., Kiffin, R., Martinez, G., Cuervo, A. M., Brown, R. H., & Glimcher, L. H. (2009) · Genes & Development · doi:10.1101/gad.1830709 · Cited by 530 · cited 4×
“Consistent with a model in which components of the ER stress response favor neurotoxicity, XBP1 deficiency in the nervous system was shown to be protective in a mouse model of ALS due to an enhanced clearance of mutant SOD1 aggregates by macroautophagy, a cellular pathway involved in protein degradation (54, 127).”
BackgroundResultInfluentialSelf-citationThe Role of Endoplasmic Reticulum Stress in the Progression of Atherosclerosis
Tabas, I. (2010) · Circulation Research · doi:10.1161/circresaha.110.224766 · Cited by 480
The differentiation and stress response factor XBP-1 drives multiple myeloma pathogenesis
Carrasco, D. R., Sukhdeo, K., Protopopova, M., Sinha, R., Enos, M., Carrasco, D. E., Zheng, M., Mani, M., Henderson, J., Pinkus, G. S., et al. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.02.015 · Cited by 414
Translational Pausing Ensures Membrane Targeting and Cytoplasmic Splicing of XBP1u mRNA
Yanagitani, K., Kimata, Y., Kadokura, H., & Kohno, K. (2011) · Science · doi:10.1126/science.1197142 · Cited by 362
Todd, D. J., McHeyzer-Williams, L. J., Kowal, C., Lee, A.-H., Volpe, B. T., Diamond, B., McHeyzer-Williams, M. G., & Glimcher, L. H. (2009) · Journal of Experimental Medicine · doi:10.1084/jem.20090738 · Cited by 233
Self-citationER Stress, Hypoxia Tolerance and Tumor Progression
Koumenis, C. (2006) · Current Molecular Medicine · doi:10.2174/156652406775574604 · Cited by 231 · cited 1×
“There is growing biomedical interest in investigating the regulatory mechanisms underlying UPR signaling and the development of strategies to target this pathway, since there is substantial evidence for the involvement of chronic ER stress in many diseases, including neurodegeneration (54, 127), diverse forms of cance…”
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Consensus guidelines for the detection of immunogenic cell death
Kepp, O., Senovilla, L., Vitale, I., Vacchelli, E., Adjemian, S., Agostinis, P., Apetoh, L., Aranda, F., Barnaba, V., Bloy, N., et al. (2014) · OncoImmunology · doi:10.4161/21624011.2014.955691 · Cited by 832
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Hetz, C., & Mollereau, B. (2014) · Nature Reviews Neuroscience · doi:10.1038/nrn3689 · Cited by 684
Self-citationGetting RIDD of RNA: IRE1 in cell fate regulation
Maurel, M., Chevet, E., Tavernier, J., & Gerlo, S. (2014) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2014.02.008 · Cited by 631
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Metadata
- Authors
- Hetz, C., Martinon, F., Rodriguez, D., & Glimcher, L. H.
- Venue
- Physiological Reviews
- Publisher
- American Physiological Society
- Published
- 2011-10
- Volume
- 91
- Issue
- 4
- Pages
- 1219-1243
- ISSN
- 0031-9333 (ISSN-L)
- 1522-1210
- OpenAlex
- W1967786181
- Cited by
- 569
- References
- 19
- FWCI
- 1.85
- Type
- journal article
- Language
- en
- Open access
- green
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