A combined "omics" approach identifies N-Myc interactor as a novel cytokine-induced regulator of IRE1α protein and c-Jun N-terminal kinase in pancreatic beta cells

Journal of Biological Chemistry

Volumn 289, Issue 30, 2014, Pages 20677-20693

  Brozzi, Flora ^a   Gerlo, Sarah ^b,c   Grieco, Fabio Arturo ^a   Nardelli, Tarlliza Romanna ^a,d   Lievens, Sam ^b,c   Gysemans, Conny ^e   Marselli, Lorella ^f   Marchetti, Piero ^f   Mathieu, Chantal ^e   Tavernier, Jan ^b,c   Eizirik, Décio L ^a  

^a UNIVERSITÉ LIBRE DE BRUXELLES   (Belgium)

^b DEPARTMENT OF PLANT SYSTEMS BIOLOGY   (Belgium)

^c GHENT UNIVERSITY   (Belgium)

^d UNIVERSITY OF CAMPINAS   (Brazil)

^e UNIVERSITY OF LEUVEN   (Belgium)

^f UNIVERSITY OF PISA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIBIOTICS; CELL DEATH; CELL MEMBRANES; CHEMICAL ACTIVATION; GLYCOPROTEINS; MAMMALS; PROTEINS;

C-JUN N-TERMINAL KINASE; ENDOPLASMIC RETICULUM STRESS; FUNCTIONAL GENOMIC ANALYSIS; NEGATIVE FEEDBACK MECHANISM; PANCREATIC BETA CELLS; PRO-INFLAMMATORY CYTOKINES; PROTEIN-PROTEIN INTERACTIONS; UNFOLDED PROTEIN RESPONSE;

CELL SIGNALING;

ERN1 PROTEIN, HUMAN; GAMMA INTERFERON; IFNG PROTEIN, HUMAN; IL1B PROTEIN, HUMAN; IL1B PROTEIN, RAT; INTERLEUKIN 1BETA; IRE1ALPHA PROTEIN, RAT; MULTIENZYME COMPLEX; NMI PROTEIN, HUMAN; PROTEIN SERINE THREONINE KINASE; RIBONUCLEASE; SIGNAL PEPTIDE; STRESS ACTIVATED PROTEIN KINASE;

AGED; ANIMAL; APOPTOSIS; CYTOLOGY; GENETICS; HEK293 CELL LINE; HUMAN; METABOLISM; MIDDLE AGED; MOUSE; PANCREAS ISLET BETA CELL; PHYSIOLOGY; RAT; UNFOLDED PROTEIN RESPONSE; WISTAR RAT;

AGED; ANIMALS; APOPTOSIS; ENDORIBONUCLEASES; HEK293 CELLS; HUMANS; INSULIN-SECRETING CELLS; INTERFERON-GAMMA; INTERLEUKIN-1BETA; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; JNK MITOGEN-ACTIVATED PROTEIN KINASES; MICE; MIDDLE AGED; MULTIENZYME COMPLEXES; PROTEIN-SERINE-THREONINE KINASES; RATS; RATS, WISTAR; UNFOLDED PROTEIN RESPONSE;

EID: 84905397729     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M114.568808     Document Type: Article

References (69)

1. Eizirik, D. L., Colli, M. L., and Ortis, F. (2009) The role of inflammation in insulitis and beta cell loss in type 1 diabetes. Nat. Rev. Endocrinol. 5, 219-226
2. Atkinson, M. A., Eisenbarth, G. S., and Michels, A. W. (2014) Type 1 diabetes. Lancet 383, 69-82
3. Santin, I., and Eizirik, D. L. (2013) Candidate genes for type 1 diabetes modulate pancreatic islet inflammation and beta cell apoptosis. Diabetes Obes. Metab. 15, 71-81
4. 2+, leading to induction of endoplasmic reticulum stress in pancreatic beta cells. Diabetes 54, 452-461
5. Allagnat, F., Fukaya, M., Nogueira, T. C., Delaroche, D., and Welsh, N. (2012) C/EBP homologous protein contributes to cytokine-induced proinflammatory responses and apoptosis in beta cells. Cell Death. Differ. 19, 1836-1846
6. Marhfour, I., Lopez, X. M., Lefkaditis, D., Salmon, I., Allagnat, F., Richardson, S. J., Morgan, N. G., and Eizirik, D. L. (2012) Expression of endoplasmic reticulum stress markers in the islets of patients with type 1 diabetes. Diabetologia 55, 2417-2420
7. Tersey, S. A., Nishiki, Y., Templin, A. T., Cabrera, S. M., Stull, N. D., Colvin, S. C., Evans-Molina, C., Rickus, J. L., Maier, B., and Mirmira, R. G. (2012) Islet beta cell endoplasmic reticulum stress precedes the onset of type 1 diabetes in the nonobese diabetic mouse model. Diabetes 61, 818-827
8. Engin, F., Yermalovich, A., Nguyen, T., Hummasti, S., Fu, W., Eizirik, D. L., Mathis, D., and Hotamisligil, G. S. (2013) Restoration of the unfolded protein response in pancreatic beta cells protects mice against type 1 diabetes. Sci. Transl. Med. 5, 10.1126/scitranslmed.3006534
9. Miani, M., Colli, M. L., Ladrière, L., Cnop, M., and Eizirik, D. L. (2012) Mild endoplasmic reticulum stress augments the proinflammatory effect of IL-1β in pancreatic rat beta cells via the IRE1α/XBP1s pathway. Endocrinology 153, 3017-3028
10. Miani, M., Barthson, J., Colli, M. L., Brozzi, F., Cnop, M., and Eizirik, D. L. (2013) Endoplasmic reticulum stress sensitizes pancreatic beta cells to interleukin-1β-induced apoptosis via Bim/A1 imbalance. Cell Death. Dis. 4, e701
11. Eizirik, D. L., Miani, M., and Cardozo, A. K. (2013) Signalling danger: endoplasmic reticulum stress and the unfolded protein response in pancreatic islet inflammation. Diabetologia 56, 234-241
12. Ron, D., and Walter, P. (2007) Signal integration in the endoplasmic reticulum unfolded protein response. Nat. Rev. Mol. Cell Biol. 8, 519-529
13. Eizirik, D. L., and Cnop, M. (2010) ER stress in pancreatic beta cells: the thin red line between adaptation and failure. Sci. Signal. 3, pe7
14. Walter, P., and Ron, D. (2011) The unfolded protein response: from stress pathway to homeostatic regulation. Science 334, 1081-1086
15. Fonseca, S. G., Gromada, J., and Urano, F. (2011) Endoplasmic reticulum stress and pancreatic beta cell death. Trends Endocrinol. Metab. 22, 266-274
16. Gurzov, E. N., and Eizirik, D. L. (2011) Bcl-2 proteins in diabetes: mitochondrial pathways of beta cell death and dysfunction. Trends Cell Biol. 21, 424-431
17. Cnop, M., Welsh, N., Jonas, J. C., Jörns, A., Lenzen, S., and Eizirik, D. L. (2005) echanisms of pancreatic beta cell death in type 1 and type 2 diabetes: many differences, few similarities. Diabetes 54, S97-S107
18. Eizirik, D. L., Cardozo, A. K., and Cnop, M. (2008) The role for endoplasmic reticulum stress in diabetes mellitus. Endocr. Rev. 29, 42-61
19. Woehlbier, U., and Hetz, C. (2011) Modulating stress responses by the UPRosome: a matter of life and death. Trends Biochem. Sci. 36, 329-337
20. Pirot, P., Naamane, N., Libert, F., Magnusson, N. E., Ørntoft, T. F., Cardozo, A. K., and Eizirik, D. L. (2007) Global profiling of genes modified by endoplasmic reticulum stress in pancreatic beta cells reveals the early degradation of insulin mRNAs. Diabetologia 50, 1006-1014
21. Lipson, K. L., Ghosh, R., and Urano, F. (2008) The role of IRE1α in the degradation of insulin mRNA in pancreatic beta cells. PLoS One 3, e1648
22. Hollien, J., and Weissman, J. S. (2006) Decay of endoplasmic reticulumlocalized mRNAs during the unfolded protein response. Science 313, 104-107
23. Urano, F., Wang, X., Bertolotti, A., Zhang, Y., Chung, P., Harding, H. P., and Ron, D. (2000) Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1. Science 287, 664-666
24. Rodriguez, D. A., Zamorano, S., Lisbona, F., Rojas-Rivera, D., Urra, H., Cubillos-Ruiz, J. R., Armisen, R., Henriquez, D. R., Cheng, E. H., Letek, M., Vaisar, T., Irrazabal, T., Gonzalez-Billault, C., Letai, A., Pimentel-Muiños, F. X., Kroemer, G., and Hetz, C. (2012) BH3-only proteins are part of a regulatory network that control the sustained signalling of the unfolded protein response sensor IRE1α. EMBO J. 31, 2322-2335
25. Qiu, Y., Mao, T., Zhang, Y., Shao, M., You, J., Ding, Q., Chen, Y., Wu, D., Xie, D., Lin, X., Gao, X., Kaufman, R. J., Li, W., and Liu, Y. (2010) A crucial role for RACK1 in the regulation of glucose-stimulated IRE1α activation in pancreatic beta cells. Sci. Signal. 3, ra7
26. Gurzov, E. N., Germano, C. M., Cunha, D. A., Ortis, F., Vanderwinden, J. M., Marchetti, P., Zhang, L., and Eizirik, D. L. (2010) p53 up-regulated modulator of apoptosis (PUMA) activation contributes to pancreatic beta cell apoptosis induced by proinflammatory cytokines and endoplasmic reticulum stress. J. Biol. Chem. 285, 19910-19920
27. Lievens, S., Vanderroost, N., Defever, D., (2012) Van der, H. J., and Tavernier, J. Array MAPPIT: a screening platform for human protein interactome analysis. Methods Mol. Biol. 812, 283-294
28. Marchetti, P., Bugliani, M., Lupi, R., Marselli, L., Masini, M., Boggi, U., Filipponi, F., Weir, G. C., Eizirik, D. L., and Cnop, M. (2007) The endoplasmic reticulum in pancreatic beta cells of type 2 diabetes patients. Diabetologia 50, 2486-2494
29. Moore, F., Colli, M. L., Cnop, M., Esteve, M. I., Cardozo, A. K., Cunha, D. A., Bugliani, M., Marchetti, P., and Eizirik, D. L. (2009) PTPN2, a candidate gene for type 1 diabetes, modulates interferon-γ-induced pancreatic beta cell apoptosis. Diabetes 58, 1283-1291
30. Eizirik, D. L., Sammeth, M., Bouckenooghe, T., Bottu, G., Sisino, G., and others (2012) The human pancreatic islet transcriptome: expression of candidate genes for type 1 diabetes and the impact of pro-inflammatory cytokines. PLoS Genet. 10.1371/journal.pgen. 1002552
31. Rasschaert, J., Ladrière, L., Urbain, M., Dogusan, Z., Katabua, B., Sato, S., Akira, S., Gysemans, C., Mathieu, C., and Eizirik, D. L. (2005) Toll-like receptor 3 and STAT-1 contribute to double-stranded RNAα interferon-γ-induced apoptosis in primary pancreatic beta cells. J. Biol. Chem. 280, 33984-33991
32. Asfari, M., Janjic, D., Meda, P., Li, G., Halban, P. A., and Wollheim, C. B. (1992) Establishment of 2-mercaptoethanol-dependent differentiated insulinsecreting cell lines. Endocrinology 130, 167-178
33. Ravassard, P., Hazhouz, Y., Pechberty, S., Bricout-Neveu, E., Armanet, M., Czernichow, P., and Scharfmann, R. (2011) A genetically engineered human pancreatic beta cell line exhibiting glucose-inducible insulin secretion. J. Clin. Invest. 121, 3589-3597
34. Grieco, F. A., Moore, F., Vigneron, F., Santin, I., Villate, O., Marselli, L., Rondas, D., Korf, H., Overbergh, L., Dotta, F., Marchetti, P., Mathieu, C., and Eizirik, D. L. (2014) IL-17A increases the expression of proinflammatory chemokines in human pancreatic islets. Diabetologia 57, 502-511
35. Eizirik, D. L., and Mandrup-Poulsen, T. (2001) A choice of death-the signal-transduction of immune-mediated beta cell apoptosis. Diabetologia 44, 2115-2133
36. Kutlu, B., Cardozo, A. K., Darville, M. I., Kruhøffer, M., Magnusson, N., Ørntoft, T., and Eizirik, D. L. (2003) Discovery of gene networks regulating cytokine-induced dysfunction and apoptosis in insulin-producing INS-1 cells. Diabetes 52, 2701-2719
37. Ortis, F., Cardozo, A. K., Crispim, D., Störling, J., Mandrup-Poulsen, T., and Eizirik, D. L. (2006) Cytokine-induced proapoptotic gene expression in insulin-producing cells is related to rapid, sustained, and nonoscillatory nuclear factor-αB activation. Mol. Endocrinol. 20, 1867-1879
38. Eizirik, D. L., Pipeleers, D. G., Ling, Z., Welsh, N., Hellerström, C., and Andersson, A. (1994) Major species differences between humans and rodents in the susceptibility to pancreatic beta cell injury. Proc. Natl. Acad. Sci. U. S. A. 91, 9253-9256
39. Eizirik, D. L., Sandler, S., Welsh, N., Cetkovic-Cvrlje, M., Nieman, A., Geller, D. A., Pipeleers, D. G., Bendtzen, K., and Hellerström, C. (1994) Cytokines suppress human islet function irrespective of their effects on nitric oxide generation. J. Clin. Invest. 93, 1968-1974
40. 2-in aqueous and protein-containing samples. Nitric Oxide 3, 225-234
41. Eyckerman, S., Verhee, A., der Heyden, J. V., Lemmens, I., Ostade, X. V., Vandekerckhove, J., and Tavernier, J. (2001) Design and application of a cytokine-receptor-based interaction trap. Nat. Cell Biol. 3, 1114-1119
42. Lievens, S., Vanderroost, N., Van der Heyden, J., Gesellchen, V., Vidal, M., and Tavernier, J. (2009) Array MAPPIT: high-throughput interactome analysis in mammalian cells. J. Proteome Res. 8, 877-886
43. Moore, F., Cunha, D. A., Mulder, H., and Eizirik, D. L. (2012) Use of RNA interference to investigate cytokine signal transduction in pancreatic beta cells. Methods Mol. Biol. 820, 179-194
44. Moore, F., Santin, I., Nogueira, T. C., Gurzov, E. N., Marselli, L., Marchetti, P., and Eizirik, D. L. (2012) The transcription factor C/EBP+ has antiapoptotic and anti-inflammatory roles in pancreatic beta cells. PLoS One 10.1371/journal.pone.0031062
45. Cunha, D. A., Hekerman, P., Ladrière, L., Bazarra-Castro, A., Ortis, F., Wakeham, M. C., Moore, F., Rasschaert, J., Cardozo, A. K., Bellomo, E., Overbergh, L., Mathieu, C., Lupi, R., Hai, T., Herchuelz, A., Marchetti, P., Rutter, G. A., Eizirik, D. L., and Cnop, M. (2008) Initiation and execution of lipotoxic ER stress in pancreatic beta cells. J. Cell Sci. 121, 2308-2318
46. Hoorens, A., Van de Casteele, M., Klöppel, G., and Pipeleers, D. (1996) Glucose promotes survival of rat pancreatic beta cells by activating synthesis of proteins which suppress a constitutive apoptotic program. J. Clin. Invest. 98, 1568-1574
47. Chen, M. C., Proost, P., Gysemans, C., Mathieu, C., and Eizirik, D. L. (2001) Monocyte chemoattractant protein-1 is expressed in pancreatic islets from prediabetic NOD mice and in interleukin-1β-exposed human and rat islet cells. Diabetologia 44, 325-332
48. Overbergh, L., Valckx, D., Waer, M., and Mathieu, C. (1999) Quantification of murine cytokine mRNAs using real time quantitative reverse transcriptase PCR. Cytokine 11, 305-312
49. Cardozo, A. K., Kruhøffer, M., Leeman, R., Orntoft, T., and Eizirik, D. L. (2001) Identification of novel cytokine-induced genes in pancreatic beta cells by high-density oligonucleotide arrays. Diabetes 50, 909-920
50. Moore, F., Naamane, N., Colli, M. L., Bouckenooghe, T., Ortis, F., Gurzov, E. N., Igoillo-Esteve, M., Mathieu, C., Bontempi, G., Thykjaer, T., Ørntoft, T. F., and Eizirik, D. L. (2011) STAT1 is a master regulator of pancreatic beta cell apoptosis and islet inflammation. J. Biol. Chem. 286, 929-941
51. Ortis, F., Naamane, N., Flamez, D., Ladrière, L., Moore, F., Cunha, D. A., Colli, M. L., Thykjaer, T., Thorsen, K., Orntoft, T. F., and Eizirik, D. L. (2010) Cytokines interleukin-1β and tumor necrosis factor-α regulate different transcriptional and alternative splicing networks in primary beta cells. Diabetes 59, 358-374
52. Tirasophon, W., Lee, K., Callaghan, B., Welihinda, A., and Kaufman, R. J. (2000) The endoribonuclease activity of mammalian IRE1 autoregulates its mRNA and is required for the unfolded protein response. Genes Dev. 14, 2725-2736
53. Bendelac, A., Carnaud, C., Boitard, C., and Bach, J. F. (1987) Syngeneic transfer of autoimmune diabetes from diabetic NOD mice to healthy neonates. Requirement for both L3T4α and Lyt-2α T cells. J. Exp. Med. 166, 823-832
54. Ammendrup, A., Maillard, A., Nielsen, K., Aabenhus Andersen, N., Serup, P., Dragsbaek Madsen, O., Mandrup-Poulsen, T., and Bonny, C. (2000) The c-Jun. amino-terminal kinase pathway is preferentially activated by interleukin-1 and controls apoptosis in differentiating pancreatic beta cells. Diabetes 49, 1468-1476
55. Bonny, C., Oberson, A., Steinmann, M., Schorderet, D. F., Nicod, P., and Waeber, G. (2000) IB1 reduces cytokine-induced apoptosis of insulinsecreting cells. J. Biol. Chem. 275, 16466-16472
56. Bonny, C., Oberson, A., Negri, S., Sauser, C., and Schorderet, D. F. (2001) Cell-permeable peptide inhibitors of JNK: novel blockers of beta cell death. Diabetes 50, 77-82
57. 2, a candidate risk gene for type 1 diabetes, regulates apoptosis in pancreatic beta cells via JNK1 modulation and crosstalk with the candidate gene PTPN2. Diabetes 63, 2516-2527
58. Gurzov, E. N., Ortis, F., Cunha, D. A., Gosset, G., Li, M., Cardozo, A. K., and Eizirik, D. L. (2009) Signaling by IL-1βαIFN-γ and ER stress converge on DP5/Hrk activation: a novel mechanism for pancreatic beta cell apoptosis. Cell Death Differ. 16, 1539-1550
59. Lee, S. I., Boyle, D. L., Berdeja, A., and Firestein, G. S. (2012) Regulation of inflammatory arthritis by the upstream kinase mitogen activated protein kinase kinase 7 in the c-Jun. N-terminal kinase pathway. Arthritis Res. Ther. 14, R38
60. Matsuzawa, A., Nishitoh, H., Tobiume, K., Takeda, K., and Ichijo, H. (2002) Physiological roles of ASK1-mediated signal transduction in oxidative stress- and endoplasmic reticulum stress-induced apoptosis: advanced findings from ASK1 knockout mice. Antioxid. Redox Signal. 4, 415-425
61. Nishitoh, H., Saitoh, M., Mochida, Y., Takeda, K., Nakano, H., Rothe, M., Miyazono, K., and Ichijo, H. (1998) ASK1 is essential for JNK/SAPK activation by TRAF2. Mol. Cell 2, 389-395
62. Han, D., Lerner, A. G., Vande Walle, L., Upton, J. P., Xu, W., Hagen, A., Backes, B. J., Oakes, S. A., and Papa, F. R. (2009) IRE1α kinase activation modes control alternate endoribonuclease outputs to determine divergent cell fates. Cell 138, 562-575
63. Santin, I., Moore, F., Colli, M. L., Gurzov, E. N., Marselli, L., Marchetti, P., and Eizirik, D. L. (2011) PTPN2, a candidate gene for type 1 diabetes, modulates pancreatic beta cell apoptosis via regulation of the BH3-only protein Bim. Diabetes 60, 3279-3288
64. Nishitoh, H., Matsuzawa, A., Tobiume, K., Saegusa, K., Takeda, K., Inoue, K., Hori, S., Kakizuka, A., and Ichijo, H. (2002) ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death triggered by expanded polyglutamine repeats. Genes Dev. 16, 1345-1355
65. Koga, S., Kojima, S., Kishimoto, T., Kuwabara, S., and Yamaguchi, A. (2012) Overexpression of MAP kinase phosphatase-1 (MKP-1) suppresses neuronal death through regulating JNK signaling in hypoxia/re-oxygenation. Brain Res. 1436, 137-146
66. Kim, K. H., An, D. R., Song, J., Yoon, J. Y., Kim, H. S., Yoon, H. J., Im, H. N., Kim, J., Kim, do, J., Lee, S. J., Kim, K. H., Lee, H. M., Kim, H. J., Jo, E. K., Lee, J. Y., and Suh, S. W. (2012) Mycobacterium tuberculosis Eis protein initiates suppression of host immune responses by acetylation of DUSP16/MKP-7. Proc. Natl. Acad. Sci. U. S. A. 109, 7729-7734
67. Lee, S., Syed, N., Taylor, J., Smith, P., Griffin, B., Baens, M., Bai, M., Bourantas, K., Stebbing, J., Naresh, K., Nelson, M., Tuthill, M., Bower, M., Hatzimichael, E., and Crook, T. (2010) DUSP16 is an epigenetically regulated determinant of JNK signalling in Burkitt's lymphoma. Br. J. Cancer 103, 265-274
68. Zhu, M., John, S., Berg, M., and Leonard, W. J. (1999) Functional association of Nmi with Stat5 and Stat1 in IL-2- and IFNγ-mediated signaling. Cell 96, 121-130
69. Gysemans, C. A., Ladrière, L., Callewaert, H., Rasschaert, J., Flamez, D., Levy, D. E., Matthys, P., Eizirik, D. L., and Mathieu, C. (2005) Disruption of the γ-interferon signaling pathway at the level of signal transducer and activator of transcription-1 prevents immune destruction of beta cells. Diabetes 54, 2396-2403