دورية أكاديمية
Ubiquitin D regulates IRE1α/c-Jun N-terminal Kinase (JNK) protein-dependent apoptosis in pancreatic beta cells
| العنوان: | Ubiquitin D regulates IRE1α/c-Jun N-terminal Kinase (JNK) protein-dependent apoptosis in pancreatic beta cells |
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| المؤلفون: | Brozzi, Flora, Gerlo, Sarah, Grieco, Fabio Arturo, Juusola, Matilda, Balhuizen, Alexander, Lievens, Sam, Gysemans, Conny, Mathieu, Chantal, Tavernier, Jan, Eizirik, Décio L., BUGLIANI, MARCO, MARCHETTI, PIERO |
| المساهمون: | Brozzi, Flora, Gerlo, Sarah, Grieco, Fabio Arturo, Juusola, Matilda, Balhuizen, Alexander, Lievens, Sam, Gysemans, Conny, Bugliani, Marco, Mathieu, Chantal, Marchetti, Piero, Tavernier, Jan, Eizirik, Décio L. |
| سنة النشر: | 2016 |
| المجموعة: | ARPI - Archivio della Ricerca dell'Università di Pisa |
| مصطلحات موضوعية: | IRE1α, apoptosi, c-Jun N-terminal kinase (JNK), cytokinesi, endoplasmic reticulum stress (ER stress), type 1 diabete, ubiquitin D, Aged, 80 and over, Animal, Blotting, Western, Cell Line, Tumor, Cells, Cultured, Cytokine, Endoribonuclease, Female, Gene Expression, HEK293 Cell, Human, Insulin-Secreting Cell, JNK Mitogen-Activated Protein Kinase, Male, Middle Aged, Protein Binding, Protein-Serine-Threonine Kinase, RNA Interference, Rat |
| الوصف: | Pro-inflammatory cytokines contribute to pancreatic beta cell apoptosis in type 1 diabetes at least in part by inducing endoplasmic reticulum (ER) stress and the consequent unfolded protein response (UPR). It remains to be determined what causes the transition from "physiological" to "apoptotic" UPR, but accumulating evidence indicates that signaling by the ER transmembrane protein IRE1α is critical for this transition. IRE1α activation is regulated by both intra-ER and cytosolic cues. We evaluated the role for the presently discovered cytokine-induced and IRE1α-interacting protein ubiquitin D (UBD) on the regulation of IRE1α and its downstream targets. UBD was identified by use of a MAPPIT (mammalian protein-protein interaction trap)-based IRE1α interactome screen followed by comparison against functional genomic analysis of human and rodent beta cells exposed to pro-inflammatory cytokines. Knockdown of UBD in human and rodent beta cells and detailed signal transduction studies indicated that UBD modulates cytokine-induced UPR/IRE1α activation and apoptosis. UBD expression is induced by the pro-inflammatory cytokines interleukin (IL)-1β and interferon (IFN)-γ in rat and human pancreatic beta cells, and it is also up-regulated in beta cells of inflamed islets from non-obese diabetic mice. UBD interacts with IRE1α in human and rodent beta cells, modulating IRE1α-dependent activation of JNK and cytokine-induced apoptosis. Our data suggest that UBD provides a negative feedback on cytokine-induced activation of the IRE1α/JNK pro-apoptotic pathway in cytokine-exposed beta cells. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | ELETTRONICO |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/27044747; info:eu-repo/semantics/altIdentifier/wos/WOS:000378092800009; volume:291; issue:23; firstpage:12040; lastpage:12056; numberofpages:17; journal:THE JOURNAL OF BIOLOGICAL CHEMISTRY; http://hdl.handle.net/11568/831808Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84974667152; http://www.jbc.org/content/291/23/12040.full.pdfTest |
| DOI: | 10.1074/jbc.M115.704619 |
| الإتاحة: | https://doi.org/10.1074/jbc.M115.704619Test http://hdl.handle.net/11568/831808Test http://www.jbc.org/content/291/23/12040.full.pdfTest |
| رقم الانضمام: | edsbas.3481B047 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1074/jbc.M115.704619 |
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