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Ubiquitin D regulates IRE1 α/c-Jun N-terminal kinase (JNK) protein-dependent apoptosis in pancreatic beta cells

(2016) JOURNAL OF BIOLOGICAL CHEMISTRY. 291(23). p.12040-12056
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Abstract
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 IRE1 alpha is critical for this transition. IRE1 alpha activation is regulated by both intra-ER and cytosolic cues. We evaluated the role for the presently discovered cytokine-induced and IRE1 alpha-interacting protein ubiquitin D (UBD) on the regulation of IRE1 alpha and its downstream targets. UBD was identified by use of a MAPPIT (mammalian protein-protein interaction trap)-based IRE1 alpha interactome screen followed by comparison against functional genomic analysis of human and rodent beta cells exposed to pro-inflammatory cytokines. Knockdown ofUBDin human and rodent beta cells and detailed signal transduction studies indicated that UBD modulates cytokine-induced UPR/IRE1 alpha activation and apoptosis. UBD expression is induced by the pro-inflammatory cytokines interleukin (IL)-1 beta and interferon (IFN)-gamma 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 IRE1 alpha in human and rodent beta cells, modulating IRE1 alpha-dependent activation of JNK and cytokine-induced apoptosis. Our data suggest that UBD provides a negative feedback on cytokine-induced activation of the IRE1 alpha/JNK pro-apoptotic pathway in cytokine-exposed beta cells.
Keywords
MAJOR HISTOCOMPATIBILITY COMPLEX, ENDOPLASMIC-RETICULUM STRESS, NECROSIS-FACTOR-ALPHA, FACTOR-KAPPA-B, INTERFERON-GAMMA, SIGNAL-TRANSDUCTION, DIABETES-MELLITUS, GENE-EXPRESSION, CANDIDATE GENE, CYTOKINES

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MLA
Brozzi, Flora et al. “Ubiquitin D Regulates IRE1 α/c-Jun N-terminal Kinase (JNK) Protein-dependent Apoptosis in Pancreatic Beta Cells.” JOURNAL OF BIOLOGICAL CHEMISTRY 291.23 (2016): 12040–12056. Print.
APA
Brozzi, Flora, Gerlo, S., Grieco, F. A., Juusola, M., Balhuizen, A., Lievens, S., Gysemans, C., et al. (2016). Ubiquitin D regulates IRE1 α/c-Jun N-terminal kinase (JNK) protein-dependent apoptosis in pancreatic beta cells. JOURNAL OF BIOLOGICAL CHEMISTRY, 291(23), 12040–12056.
Chicago author-date
Brozzi, Flora, Sarah Gerlo, Fabio Arturo Grieco, Matilda Juusola, Alexander Balhuizen, Sam Lievens, Conny Gysemans, et al. 2016. “Ubiquitin D Regulates IRE1 α/c-Jun N-terminal Kinase (JNK) Protein-dependent Apoptosis in Pancreatic Beta Cells.” Journal of Biological Chemistry 291 (23): 12040–12056.
Chicago author-date (all authors)
Brozzi, Flora, Sarah Gerlo, Fabio Arturo Grieco, Matilda Juusola, Alexander Balhuizen, Sam Lievens, Conny Gysemans, Marco Bugliani, Chantal Mathieu, Piero Marchetti, Jan Tavernier, and Décio L Eizirik. 2016. “Ubiquitin D Regulates IRE1 α/c-Jun N-terminal Kinase (JNK) Protein-dependent Apoptosis in Pancreatic Beta Cells.” Journal of Biological Chemistry 291 (23): 12040–12056.
Vancouver
1.
Brozzi F, Gerlo S, Grieco FA, Juusola M, Balhuizen A, Lievens S, et al. Ubiquitin D regulates IRE1 α/c-Jun N-terminal kinase (JNK) protein-dependent apoptosis in pancreatic beta cells. JOURNAL OF BIOLOGICAL CHEMISTRY. 2016;291(23):12040–56.
IEEE
[1]
F. Brozzi et al., “Ubiquitin D regulates IRE1 α/c-Jun N-terminal kinase (JNK) protein-dependent apoptosis in pancreatic beta cells,” JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 291, no. 23, pp. 12040–12056, 2016.
@article{8060494,
  abstract     = {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 IRE1 alpha is critical for this transition. IRE1 alpha activation is regulated by both intra-ER and cytosolic cues. We evaluated the role for the presently discovered cytokine-induced and IRE1 alpha-interacting protein ubiquitin D (UBD) on the regulation of IRE1 alpha and its downstream targets. UBD was identified by use of a MAPPIT (mammalian protein-protein interaction trap)-based IRE1 alpha interactome screen followed by comparison against functional genomic analysis of human and rodent beta cells exposed to pro-inflammatory cytokines. Knockdown ofUBDin human and rodent beta cells and detailed signal transduction studies indicated that UBD modulates cytokine-induced UPR/IRE1 alpha activation and apoptosis. UBD expression is induced by the pro-inflammatory cytokines interleukin (IL)-1 beta and interferon (IFN)-gamma 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 IRE1 alpha in human and rodent beta cells, modulating IRE1 alpha-dependent activation of JNK and cytokine-induced apoptosis. Our data suggest that UBD provides a negative feedback on cytokine-induced activation of the IRE1 alpha/JNK pro-apoptotic pathway in cytokine-exposed beta cells.},
  author       = {Brozzi, Flora and Gerlo, Sarah and Grieco, Fabio Arturo and Juusola, Matilda and Balhuizen, Alexander and Lievens, Sam and Gysemans, Conny and Bugliani, Marco and Mathieu, Chantal and Marchetti, Piero and Tavernier, Jan and Eizirik, Décio L},
  issn         = {0021-9258},
  journal      = {JOURNAL OF BIOLOGICAL CHEMISTRY},
  keywords     = {MAJOR HISTOCOMPATIBILITY COMPLEX,ENDOPLASMIC-RETICULUM STRESS,NECROSIS-FACTOR-ALPHA,FACTOR-KAPPA-B,INTERFERON-GAMMA,SIGNAL-TRANSDUCTION,DIABETES-MELLITUS,GENE-EXPRESSION,CANDIDATE GENE,CYTOKINES},
  language     = {eng},
  number       = {23},
  pages        = {12040--12056},
  title        = {Ubiquitin D regulates IRE1 α/c-Jun N-terminal kinase (JNK) protein-dependent apoptosis in pancreatic beta cells},
  url          = {http://dx.doi.org/10.1074/jbc.M115.704619},
  volume       = {291},
  year         = {2016},
}

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