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SUMO4-Encoded Genetic Susceptibility to Type 1 Diabetes

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SUMO Regulation of Cellular Processes

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Abstract

Susceptibility to type 1 diabetes (T1D) is determined by interactions of multiple genes with environmental triggers. Thus far, more than 20 T1D susceptibility regions have been suggested from genetic studies by employing either genome-wide or candidate gene approaches. Because of the lack of a linear correlation between the presence of risk genes and the onset of disease, the exact susceptibility genes encoded in these regions remain largely elusive. In 2004, we first reported the cloning of a novel small ubiquitin-like modifier (SUMO) gene, SUMO4, in the IDDM5 region on chromosome 6q25, and presented strong genetic and functional evidence suggesting that SUMO4 could be a novel T1D susceptibility gene. Follow up studies have consistently confirmed this association in multiple Asian populations despite controversial observations in Caucasians which could be caused by genetic heterogeneity. In this chapter, we will summarize and validate genetic data for SUMO4 association studies in type 1 diabetes. The functional properties and possible molecular mechanisms by which SUMO4 implicates in the pathogenesis of type 1 diabetes will be also discussed based on published data.

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Abbreviations

SUMO:

Small ubiquitin-like modifier

T1D:

Type 1 diabetes

IDDM:

insulin dependent diabetes mellitus

SNP:

single-nucleotide polymorphism

NOD mouse:

nonobese diabetic mouse

STAT:

signal transducer and activator of transcription

PIAS1:

protein inhibitor of activated STAT1

AP-1:

activator protein-1

ROS:

reactive oxygen species

NO:

nitrite oxide

DCs:

dendritic cells

Tregs:

regulatory T cells

References

  • Ameyar, M., Wisniewska, M. and Weitzman, J. B., 2003, A role for AP-1 in apoptosis: the case for and against. Biochimie 85, 747–752.

    PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • Anselmino, M., Gohlke, H., Mellbin, L. and Ryden, L., 2008, Cardiovascular prevention in patients with diabetes and prediabetes. Herz 33, 170–177.

    PubMed  Google Scholar 

  • Atkinson, M. A., 2005, ADA Outstanding Scientific Achievement Lecture 2004. Thirty years of investigating the autoimmune basis for type 1 diabetes: why can't we prevent or reverse this disease? Diabetes 54, 1253–1263.

    PubMed  CAS  Google Scholar 

  • Babic, I., Cherry, E. and Fujita, D. J., 2006, SUMO modification of Sam68 enhances its ability to repress cyclin D1 expression and inhibits its ability to induce apoptosis. Oncogene 25, 4955–4964.

    PubMed  CAS  Google Scholar 

  • Bach, J. F., Garchon, H. J. and van, Endert P., 2001, Genetics of human type 1 diabetes mellitus. Curr. Dir. Autoimmun. 4, 1–30.

    PubMed  CAS  Google Scholar 

  • Bacher, S. and Schmitz, M. L., 2004, The NF-kappaB pathway as a potential target for autoimmune disease therapy. Curr. Pharm. Des. 10, 2827–2837.

    PubMed  CAS  Google Scholar 

  • Bandurska-Stankiewicz, E. and Wiatr, D., 2007, [Programme preventing vision loss due to diabetes]. Klin. Oczna. 109, 359–362.

    PubMed  Google Scholar 

  • Berberich-Siebelt, F., Berberich, I., Andrulis, M., Santner-Nanan, B., Jha, M. K., Klein-Hessling, S., Schimpl, A. and Serfling, E., 2006, SUMOylation interferes with CCAAT/enhancer-binding protein beta-mediated c-myc repression, but not IL-4 activation in T cells. J. Immunol. 176, 4843–4851.

    PubMed  CAS  Google Scholar 

  • Bischof, O., Schwamborn, K., Martin, N., Werner, A., Sustmann, C., Grosschedl, R. and Dejean, A., 2006, The E3 SUMO ligase PIASy is a regulator of cellular senescence and apoptosis. Mol. Cell 22, 783–794.

    PubMed  CAS  Google Scholar 

  • Bohren, K. M., Nadkarni, V., Song, J. H., Gabbay, K. H. and Owerbach, D., 2004, A M55V polymorphism in a novel SUMO gene (SUMO-4) differentially activates heat shock transcription factors and is associated with susceptibility to type I diabetes mellitus. J. Biol. Chem. 279, 27233–27238.

    PubMed  CAS  Google Scholar 

  • Bossis, G., Malnou, C. E., Farras, R., Andermarcher, E., Hipskind, R., Rodriguez, M., Schmidt, D., Muller, S., Jariel-Encontre, I. and Piechaczyk, M., 2005, Down-regulation of c-Fos/c-Jun AP-1 dimer activity by sumoylation. Mol. Cell. Biol. 25, 6964–6979.

    PubMed  CAS  Google Scholar 

  • Boulton, A. J., 2007, Diabetic neuropathy: classification, measurement and treatment. Curr. Opin. Endocrinol. Diabetes Obes. 14, 141–145.

    PubMed  Google Scholar 

  • Brilot, F. and Geenen, V., 2005, [Role of viral infections in the pathogenesis of type 1 diabetes]. Rev. Med. Liege. 60, 297–302.

    PubMed  CAS  Google Scholar 

  • Cameron, M. J., Arreaza, G. A., Zucker, P., Chensue, S. W., Strieter, R. M., Chakrabarti, S. and Delovitch, T. L., 1997, IL-4 prevents insulitis and insulin-dependent diabetes mellitus in nonobese diabetic mice by potentiation of regulatory T helper-2 cell function. J. Immunol. 159, 4686–4692.

    PubMed  CAS  Google Scholar 

  • Chanda, S. K., White, S., Orth, A. P., Reisdorph, R., Miraglia, L., Thomas, R. S., DeJesus, P., Mason, D. E., Huang, Q., Vega, R., Yu, D. H., Nelson, C. G., Smith, B. M., Terry, R., Linford, A. S., Yu, Y., Chirn, G. W., Song, C., Labow, M. A., Cohen, D., King, F. J., Peters, E. C., Schultz, P. G., Vogt, P. K., Hogenesch, J. B. and Caldwell, J. S., 2003, Genome-scale functional profiling of the mammalian AP-1 signaling pathway. Proc. Natl. Acad. Sci. U.S.A. 100, 12153–12158.

    PubMed  CAS  Google Scholar 

  • Chang, L. and Karin, M., 2001, Mammalian MAP kinase signalling cascades. Nature 410, 37–40.

    PubMed  CAS  Google Scholar 

  • Chen, C. Y., Del Gatto-Konczak, F., Wu, Z. and Karin, M., 1998, Stabilization of interleukin-2 mRNA by the c-Jun NH2-terminal kinase pathway. Science 280, 1945–1949.

    PubMed  CAS  Google Scholar 

  • Chen, G., Hohmeier, H. E. and Newgard, C. B., 2001, Expression of the transcription factor STAT-1 alpha in insulinoma cells protects against cytotoxic effects of multiple cytokines. J. Biol. Chem. 276, 766–772.

    PubMed  CAS  Google Scholar 

  • Chen, J., Lu, Y., Lee, C. H., Li, R., Leiter, E. H. and Mathews, C. E., 2008, Commonalities of genetic resistance to spontaneous autoimmune and free radical-mediated diabetes. Free Radic. Biol. Med. 45,1263–1270.

    PubMed  CAS  Google Scholar 

  • Cheung, N. and Wong, T. Y., 2008, Diabetic retinopathy and systemic vascular complications. Prog. Retin. Eye Res. 27, 161–176.

    PubMed  CAS  Google Scholar 

  • Chiu, H. K. and Palmer, J. P., 2004, Autoimmune diabetes: more than just one flavor? J. Endocrinol. Invest. 27, 480–484.

    PubMed  CAS  Google Scholar 

  • Christen, U., 2007, Chemokines as drug targets in type 1 diabetes. Endocr. Metab Immune. Disord. Drug Targets 7, 7–12.

    PubMed  CAS  Google Scholar 

  • Cnop, M., Welsh, N., Jonas, J. C., Jorns, A., Lenzen, S. and Eizirik, D. L., 2005, Mechanisms of pancreatic beta-cell death in type 1 and type 2 diabetes: many differences, few similarities. Diabetes 54 (Suppl 2), S97–S107.

    PubMed  CAS  Google Scholar 

  • Cornell, R. S. and Ducic, I., 2008, Painful diabetic neuropathy. Clin. Podiatr. Med. Surg. 25, 347–360.

    PubMed  Google Scholar 

  • Couch, R., Jetha, M., Dryden, D. M., Hooten, N., Liang, Y., Durec, T., Sumamo, E., Spooner, C., Milne, A., O’Gorman, K. and Klassen, T. P., 2008, Diabetes education for children with type 1 diabetes mellitus and their families. Evid. Rep. Technol. Assess.(Full.Rep.). 166, 1–144.

    Google Scholar 

  • Darville, M. I. and Eizirik, D. L., 1998, Regulation by cytokines of the inducible nitric oxide synthase promoter in insulin-producing cells. Diabetologia 41, 1101–1108.

    PubMed  CAS  Google Scholar 

  • Davies, J. L., Cucca, F., Goy, J. V., Atta, Z. A., Merriman, M. E., Wilson, A., Barnett, A. H., Bain, S. C. and Todd, J. A., 1996, Saturation multipoint linkage mapping of chromosome 6q in type 1 diabetes. Hum. Mol. Genet. 5, 1071–1074.

    PubMed  CAS  Google Scholar 

  • Davies, J. L., Kawaguchi, Y., Bennett, S. T., Copeman, J. B., Cordell, H. J., Pritchard, L. E., Reed, P. W., Gough, S. C., Jenkins, S. C., Palmer, S. M., et al., 1994, A genome-wide search for human type 1 diabetes susceptibility genes. Nature 371, 130–136.

    PubMed  CAS  Google Scholar 

  • Delepine, M., Pociot, F., Habita, C., Hashimoto, L., Froguel, P., Rotter, J., Cambon-Thomsen, A., Deschamps, I., Djoulah, S., Weissenbach, J., Nerup, J., Lathrop, M. and Julier, C., 1997, Evidence of a non-MHC susceptibility locus in type I diabetes linked to HLA on chromosome 6. Am. J. Hum. Genet. 60, 174–187.

    PubMed  CAS  Google Scholar 

  • Deng, Z., Wan, M. and Sui, G., 2007, PIASy-mediated sumoylation of Yin Yang 1 depends on their interaction but not the RING finger. Mol. Cell. Biol. 27, 3780–3792.

    PubMed  CAS  Google Scholar 

  • Desterro, J. M., Rodriguez, M. S. and Hay, R. T., 1998, SUMO-1 modification of IkappaBalpha inhibits NF-kappaB activation. Mol. Cell 2, 233–239.

    PubMed  CAS  Google Scholar 

  • Eferl, R., Sibilia, M., Hilberg, F., Fuchsbichler, A., Kufferath, I., Guertl, B., Zenz, R., Wagner, E. F. and Zatloukal, K., 1999, Functions of c-Jun in liver and heart development. J. Cell Biol. 145, 1049–1061.

    PubMed  CAS  Google Scholar 

  • Ehninger, A., Mziaut, H. and Solimena, M., 2007, Emerging role of SUMO in pancreatic beta-cells. Horm. Metab. Res. 39, 658–664.

    PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • El-Osta, A., Brasacchio, D., Yao, D., Pocai, A., Jones, P. L., Roeder, R. G., Cooper, M. E. and Brownlee, M., 2008, Transient high glucose causes persistent epigenetic changes and altered gene expression during subsequent normoglycemia. J. Exp. Med. 205, 2409–2417.

    PubMed  CAS  Google Scholar 

  • Feltbower, R. G., McKinney, P. A., Parslow, R. C., Stephenson, C. R. and Bodansky, H. J., 2003, Type 1 diabetes in Yorkshire, UK: time trends in 0-14 and 15-29-year-olds, age at onset and age-period-cohort modelling. Diabet. Med. 20, 437–441.

    PubMed  CAS  Google Scholar 

  • Filippi, C. M. and von Herrath, M. G., 2008, Viral trigger for type 1 diabetes: pros and cons. Diabetes 57, 2863–2871.

    PubMed  CAS  Google Scholar 

  • Flodstrom-Tullberg, M., Yadav, D., Hagerkvist, R., Tsai, D., Secrest, P., Stotland, A. and Sarvetnick, N., 2003, Target cell expression of suppressor of cytokine signaling-1 prevents diabetes in the NOD mouse. Diabetes 52, 2696–2700.

    PubMed  Google Scholar 

  • Fox, C. J. and Danska, J. S., 1997, IL-4 expression at the onset of islet inflammation predicts nondestructive insulitis in nonobese diabetic mice. J. Immunol. 158, 2414–2424.

    PubMed  CAS  Google Scholar 

  • Fraga, M. F., Ballestar, E., Paz, M. F., Ropero, S., Setien, F., Ballestar, M. L., Heine-Suner, D., Cigudosa, J. C., Urioste, M., Benitez, J., Boix-Chornet, M., Sanchez-Aguilera, A., Ling, C., Carlsson, E., Poulsen, P., Vaag, A., Stephan, Z., Spector, T. D., Wu, Y. Z., Plass, C. and Esteller, M., 2005, Epigenetic differences arise during the lifetime of monozygotic twins. Proc. Natl. Acad. Sci. U.S.A. 102, 10604–10609.

    PubMed  CAS  Google Scholar 

  • Funakoshi-Tago, M., Tago, K., Sonoda, Y., Tominaga, S. and Kasahara, T., 2003, TRAF6 and C-SRC induce synergistic AP-1 activation via PI3-kinase-AKT-JNK pathway. Eur. J. Biochem. 270, 1257–1268.

    PubMed  CAS  Google Scholar 

  • Garaude, J., Farras, R., Bossis, G., Charni, S., Piechaczyk, M., Hipskind, R. A. and Villalba, M., 2008, SUMOylation regulates the transcriptional activity of JunB in T lymphocytes. J. Immunol. 180, 5983–5990.

    PubMed  CAS  Google Scholar 

  • Gardner, S. E. and Frantz, R. A., 2008, Wound bioburden and infection-related complications in diabetic foot ulcers. Biol. Res. Nurs. 10, 44–53.

    PubMed  Google Scholar 

  • Gillespie, K. M., 2006, Type 1 diabetes: pathogenesis and prevention. Can. Med. J. Assoc. 175, 165–170.

    Google Scholar 

  • Giorgino, F., de Robertis O., Laviola, L., Montrone, C., Perrini, S., McCowen, K. C. and Smith, R. J., 2000, The sentrin-conjugating enzyme mUbc9 interacts with GLUT4 and GLUT1 glucose transporters and regulates transporter levels in skeletal muscle cells. Proc. Natl. Acad. Sci. U.S.A. 97, 1125–1130.

    PubMed  CAS  Google Scholar 

  • Gomes, M. V. and Waterland, R. A., 2008, Individual epigenetic variation: when, why, and so what? Nestle. Nutr. Workshop Ser. Pediatr. Program 62, 141–150.

    PubMed  CAS  Google Scholar 

  • Graser, R. T., Mathews, C. E., Leiter, E. H. and Serreze, D. V., 1999, MHC characterization of ALR and ALS mice: respective similarities to the NOD and NON strains. Immunogenetics 49, 722–726.

    PubMed  CAS  Google Scholar 

  • Green, A., Gale, E. A. and Patterson, C. C., 1992, Incidence of childhood-onset insulin-dependent diabetes mellitus: the EURODIAB ACE Study. Lancet 339, 905–909.

    PubMed  CAS  Google Scholar 

  • Griffiths, H. R., 2005, ROS as signalling molecules in T cells – evidence for abnormal redox signalling in the autoimmune disease, rheumatoid arthritis. Redox. Rep. 10, 273–280.

    PubMed  CAS  Google Scholar 

  • Guerrero-Bosagna, C. M., Sabat, P., Valdovinos, F. S., Valladares, L. E. and Clark, S. J., 2008, Epigenetic and phenotypic changes result from a continuous pre and post natal dietary exposure to phytoestrogens in an experimental population of mice. BMC Physiol. 8, 17.

    PubMed  Google Scholar 

  • Guil, S. and Esteller, M., 2008, DNA methylomes, histone codes and miRNAs: tying it all together. Int. J. Biochem. Cell Biol. 41, 87–95.

    PubMed  Google Scholar 

  • Guo, D., Han, J., Adam, B. L., Colburn, N. H., Wang, M. H., Dong, Z., Eizirik, D. L., She, J. X. and Wang, C. Y., 2005, Proteomic analysis of SUMO4 substrates in HEK293 cells under serum starvation-induced stress. Biochem. Biophys. Res. Commun. 337, 1308–1318.

    PubMed  CAS  Google Scholar 

  • Guo, D., Li, M., Zhang, Y., Yang, P., Eckenrode, S., Hopkins, D., Zheng, W., Purohit, S., Podolsky, R. H., Muir, A., Wang, J., Dong, Z., Brusko, T., Atkinson, M., Pozzilli, P., Zeidler, A., Raffel, L. J., Jacob, C. O., Park, Y., Serrano-Rios, M., Larrad, M. T., Zhang, Z., Garchon, H. J., Bach, J. F., Rotter, J. I., She, J. X. and Wang, C. Y., 2004, A functional variant of SUMO4, a new I kappa B alpha modifier, is associated with type 1 diabetes. Nat. Genet. 36, 837–841.

    PubMed  CAS  Google Scholar 

  • Gurzov, E. N., Ortis, F., Bakiri, L., Wagner, E. F. and Eizirik, D. L., 2008, JunB Inhibits ER Stress and Apoptosis in Pancreatic Beta Cells. PLoS. ONE 3, e3030.

    PubMed  Google Scholar 

  • Hayashi, T. and Faustman, D., 2000, A role for NF-kappaB and the proteasome in autoimmunity. Arch. Immunol. Ther. Exp.(Warsz.) 48, 353–365.

    CAS  Google Scholar 

  • Hirschhorn, J. N., 2003, Genetic epidemiology of type 1 diabetes. Pediatr.Diabetes 4, 87–100.

    PubMed  Google Scholar 

  • Ho, E. and Bray, T. M., 1999, Antioxidants, NFkappaB activation, and diabetogenesis. Proc. Soc. Exp. Biol. Med. 222, 205–213.

    PubMed  CAS  Google Scholar 

  • Hoffmann, A. and Baltimore, D., 2006, Circuitry of nuclear factor kappaB signaling. Immunol. Rev. 210, 171–186.

    PubMed  Google Scholar 

  • Hohmeier, H. E., Thigpen, A., Tran, V. V., Davis, R. and Newgard, C. B., 1998, Stable expression of manganese superoxide dismutase (MnSOD) in insulinoma cells prevents IL-1beta- induced cytotoxicity and reduces nitric oxide production. J. Clin. Invest. 101, 1811–1820.

    PubMed  CAS  Google Scholar 

  • Hou, S., Yang, P., Du, L., Zhou, H., Lin, X., Liu, X. and Kijlstra, A., 2008, SUMO4 gene polymorphisms in Chinese Han patients with Behcet's disease. Clin. Immunol. 129, 170–175.

    PubMed  CAS  Google Scholar 

  • Inoguchi, T. and Takayanagi, R., 2008, [Role of oxidative stress in diabetic vascular complications]. Fukuoka Igaku Zasshi 99, 47–55.

    PubMed  CAS  Google Scholar 

  • Isogai, S. and Shirakawa, M., 2007, [Protein modification by SUMO]. Seikagaku 79, 1120–1130.

    PubMed  CAS  Google Scholar 

  • Jackson, P. K., 2001, A new RING for SUMO: wrestling transcriptional responses into nuclear bodies with PIAS family E3 SUMO ligases. Genes Dev. 15, 3053–3058.

    PubMed  CAS  Google Scholar 

  • Jarosz-Chobot, P., Otto-Buczkowska, E. and Koehler, B., 2000, The increased trend of type 1 diabetes mellitus in children (0-14 years) in the Upper Silesia region of Poland. Acta Paediatr. 89, 120.

    PubMed  CAS  Google Scholar 

  • Johnson, E. S., 2004, Protein modification by SUMO. Annu.Rev.Biochem. 73, 355–382.

    PubMed  CAS  Google Scholar 

  • Kaneto, H., Katakami, N., Kawamori, D., Miyatsuka, T., Sakamoto, K., Matsuoka, T. A., Matsuhisa, M. and Yamasaki, Y., 2007a, Involvement of oxidative stress in the pathogenesis of diabetes. Antioxid. Redox. Signal 9, 355–366.

    PubMed  CAS  Google Scholar 

  • Kaneto, H., Matsuoka, T. A., Katakami, N., Kawamori, D., Miyatsuka, T., Yoshiuchi, K., Yasuda, T., Sakamoto, K., Yamasaki, Y. and Matsuhisa, M., 2007b, Oxidative stress and the JNK pathway are involved in the development of type 1 and type 2 diabetes. Curr. Mol. Med. 7, 674–686.

    PubMed  CAS  Google Scholar 

  • Katarina, K., Daniela, P., Peter, N., Marianna, R., Pavlina, C., Stepanka, P., Jan, L., Ludmila, T., Michal, A. and Marie, C., 2007, HLA, NFKB1 and NFKBIA gene polymorphism profile in autoimmune diabetes mellitus patients. Exp. Clin. Endocrinol. Diabetes 115, 124–129.

    PubMed  CAS  Google Scholar 

  • Kawasaki, E., Abiru, N. and Eguchi, K., 2004, Prevention of type 1 diabetes: from the view point of beta cell damage. Diabetes Res. Clin. Pract. 66 (Suppl 1), S27–S32.

    PubMed  CAS  Google Scholar 

  • Kay, T. W., Thomas, H. E., Harrison, L. C. and Allison, J., 2000, The beta cell in autoimmune diabetes: many mechanisms and pathways of loss. Trends Endocrinol. Metab. 11, 11–15.

    PubMed  CAS  Google Scholar 

  • Kim, S., Millet, I., Kim, H. S., Kim, J. Y., Han, M. S., Lee, M. K., Kim, K. W., Sherwin, R. S., Karin, M. and Lee, M. S., 2007, NF-kappa B prevents beta cell death and autoimmune diabetes in NOD mice. Proc. Natl. Acad. Sci. U.S.A. 104, 1913–1918.

    PubMed  CAS  Google Scholar 

  • Kishi, A., Nakamura, T., Nishio, Y., Maegawa, H. and Kashiwagi, A., 2003, Sumoylation of Pdx1 is associated with its nuclear localization and insulin gene activation. Am. J. Physiol. Endocrinol. Metab. 284, E830–E840.

    PubMed  CAS  Google Scholar 

  • Kisseleva, T., Bhattacharya, S., Braunstein, J. and Schindler, C. W., 2002, Signaling through the JAK/STAT pathway, recent advances and future challenges. Gene 285, 1–24.

    PubMed  CAS  Google Scholar 

  • Knip, M. and Akerblom, H. K., 1999, Environmental factors in the pathogenesis of type 1 diabetes mellitus. Exp. Clin. Endocrinol. Diabetes 107 (Suppl 3), S93–S100.

    PubMed  CAS  Google Scholar 

  • Kotaja, N., Karvonen, U., Janne, O. A. and Palvimo, J. J., 2002, PIAS proteins modulate transcription factors by functioning as SUMO-1 ligases. Mol. Cell. Biol. 22, 5222–5234.

    PubMed  CAS  Google Scholar 

  • Kurrer, M. O., Pakala, S. V., Hanson, H. L. and Katz, J. D., 1997, Beta cell apoptosis in T cell-mediated autoimmune diabetes. Proc. Natl. Acad. Sci. U.S.A. 94, 213–218.

    PubMed  CAS  Google Scholar 

  • Kyvik, K. O., Green, A. and Beck-Nielsen, H., 1995, Concordance rates of insulin dependent diabetes mellitus: a population based study of young Danish twins. Brit. Med. J. 311, 913–917.

    PubMed  CAS  Google Scholar 

  • Lalioti, V. S., Vergarajauregui, S., Pulido, D. and Sandoval, I. V., 2002, The insulin-sensitive glucose transporter, GLUT4, interacts physically with Daxx. Two proteins with capacity to bind Ubc9 and conjugated to SUMO1. J. Biol. Chem. 277, 19783–19791.

    PubMed  CAS  Google Scholar 

  • Lamb, W. H., 1994, Childhood diabetes. Br. J. Hosp. Med. 51, 471–475.

    PubMed  CAS  Google Scholar 

  • Lamhamedi-Cherradi, S. E., Zheng, S., Hilliard, B. A., Xu, L., Sun, J., Alsheadat, S., Liou, H. C. and Chen, Y. H., 2003, Transcriptional regulation of type I diabetes by NF-kappa B. J. Immunol. 171, 4886–4892.

    PubMed  CAS  Google Scholar 

  • Larbi, A., Kempf, J. and Pawelec, G., 2007, Oxidative stress modulation and T cell activation. Exp. Gerontol. 42, 852–858.

    PubMed  CAS  Google Scholar 

  • Lee, S. M., Gao, B. and Fang, D., 2008, FoxP3 maintains Treg unresponsiveness by selectively inhibiting the promoter DNA-binding activity of AP-1. Blood 111, 3599–3606.

    PubMed  CAS  Google Scholar 

  • Lee, Y. S., Jang, M. S., Lee, J. S., Choi, E. J. and Kim, E., 2005, SUMO-1 represses apoptosis signal-regulating kinase 1 activation through physical interaction and not through covalent modification. EMBO Rep. 6, 949–955.

    PubMed  CAS  Google Scholar 

  • Lgssiar, A., Hassan, M., Schott-Ohly, P., Friesen, N., Nicoletti, F., Trepicchio, W. L. and Gleichmann, H., 2004, Interleukin-11 inhibits NF-kappaB and AP-1 activation in islets and prevents diabetes induced with streptozotocin in mice. Exp. Biol. Med. 229, 425–436.

    CAS  Google Scholar 

  • Li, M., Guo, D., Isales, C. M., Eizirik, D. L., Atkinson, M., She, J. X. and Wang, C. Y., 2005, SUMO wrestling with type 1 diabetes. J. Mol. Med. 83, 504–513.

    PubMed  CAS  Google Scholar 

  • Lin, H. Y., Wang, C. L., Hsiao, P. J., Lu, Y. C., Chen, S. Y., Lin, K. D., Hsin, S. C., Hsieh, M. C. and Shin, S. J., 2007, SUMO4 M55V variant is associated with diabetic nephropathy in type 2 diabetes. Diabetes 56, 1177–1180.

    PubMed  CAS  Google Scholar 

  • Liu, L. B., Omata, W., Kojima, I. and Shibata, H., 2007, The SUMO conjugating enzyme Ubc9 is a regulator of GLUT4 turnover and targeting to the insulin-responsive storage compartment in 3T3-L1 adipocytes. Diabetes 56, 1977–1985.

    PubMed  CAS  Google Scholar 

  • Lortz, S. and Tiedge, M., 2003, Sequential inactivation of reactive oxygen species by combined overexpression of SOD isoforms and catalase in insulin-producing cells. Free Radic. Biol. Med. 34, 683–688.

    PubMed  CAS  Google Scholar 

  • Lortz, S., Tiedge, M., Nachtwey, T., Karlsen, A. E., Nerup, J. and Lenzen, S., 2000, Protection of insulin-producing RINm5F cells against cytokine-mediated toxicity through overexpression of antioxidant enzymes. Diabetes 49, 1123–1130.

    PubMed  CAS  Google Scholar 

  • Lu, S. P., Lin Feng, M. H., Huang, H. L., Huang, Y. C., Tsou, W. I. and Lai, M. Z., 2007, Reactive oxygen species promote raft formation in T lymphocytes. Free Radic. Biol. Med. 42, 936–944.

    PubMed  CAS  Google Scholar 

  • Luo, D. F., Bui, M. M., Muir, A., Maclaren, N. K., Thomson, G. and She, J. X., 1995, Affected-sib-pair mapping of a novel susceptibility gene to insulin-dependent diabetes mellitus (IDDM8) on chromosome 6q25-q27. Am. J. Hum. Genet. 57, 911–919.

    PubMed  CAS  Google Scholar 

  • Luo, D. F., Buzzetti, R., Rotter, J. I., Maclaren, N. K., Raffel, L. J., Nistico, L., Giovannini, C., Pozzilli, P., Thomson, G. and She, J. X., 1996, Confirmation of three susceptibility genes to insulin-dependent diabetes mellitus: IDDM4, IDDM5 and IDDM8. Hum. Mol. Genet. 5, 693–698.

    PubMed  CAS  Google Scholar 

  • Ma, L., Qian, S., Liang, X., Wang, L., Woodward, J. E., Giannoukakis, N., Robbins, P. D., Bertera, S., Trucco, M., Fung, J. J. and Lu, L., 2003, Prevention of diabetes in NOD mice by administration of dendritic cells deficient in nuclear transcription factor-kappaB activity. Diabetes 52, 1976–1985.

    PubMed  CAS  Google Scholar 

  • Mabley, J. G., Hasko, G., Liaudet, L., Soriano, F., Southan, G. J., Salzman, A. L. and Szabo, C., 2002, NFkappaB1 (p50)-deficient mice are not susceptible to multiple low-dose streptozotocin-induced diabetes. J. Endocrinol. 173, 457–464.

    PubMed  CAS  Google Scholar 

  • Malgrange, D., 2008, [Physiopathology of the diabetic foot]. Rev. Med. Interne. 29 (Suppl 2), S231–S237.

    PubMed  Google Scholar 

  • Manza, L. L., Codreanu, S. G., Stamer, S. L., Smith, D. L., Wells, K. S., Roberts, R. L. and Liebler, D. C., 2004, Global shifts in protein sumoylation in response to electrophile and oxidative stress. Chem. Res. Toxicol. 17, 1706–1715.

    PubMed  CAS  Google Scholar 

  • Marrero, M. B., Banes-Berceli, A. K., Stern, D. M. and Eaton, D. C., 2006, Role of the JAK/STAT signaling pathway in diabetic nephropathy. Am. J. Physiol. Renal Physiol. 290, F762–F768.

    PubMed  CAS  Google Scholar 

  • Marwick, T. H., 2008, Diabetic heart disease. Postgrad. Med. J. 84, 188–192.

    PubMed  CAS  Google Scholar 

  • Mathews, C. E., Suarez-Pinzon, W. L., Baust, J. J., Strynadka, K., Leiter, E. H. and Rabinovitch, A., 2005, Mechanisms underlying resistance of pancreatic islets from ALR/Lt mice to cytokine-induced destruction. J. Immunol. 175, 1248–1256.

    PubMed  CAS  Google Scholar 

  • Matsuzaki, K., Minami, T., Tojo, M., Honda, Y., Uchimura, Y., Saitoh, H., Yasuda, H., Nagahiro, S., Saya, H. and Nakao, M., 2003, Serum response factor is modulated by the SUMO-1 conjugation system. Biochem. Biophys. Res. Commun. 306, 32–38.

    PubMed  CAS  Google Scholar 

  • Melloul, D., 2008, Role of NF-kappaB in beta-cell death. Biochem. Soc. Trans. 36, 334–339.

    PubMed  CAS  Google Scholar 

  • Mollah, Z. U., Pai, S., Moore, C., O'Sullivan, B. J., Harrison, M. J., Peng, J., Phillips, K., Prins, J. B., Cardinal, J. and Thomas, R., 2008, Abnormal NF-kappa B function characterizes human type 1 diabetes dendritic cells and monocytes. J. Immunol. 180, 3166–3175.

    PubMed  CAS  Google Scholar 

  • Monhart, V., 2008, [Diabetes mellitus, hypertension and kidney]. Vnitr. Lek. 54, 499–504, 507.

    PubMed  CAS  Google Scholar 

  • Morton, N. M., de Groot, R. P., Cawthorne, M. A. and Emilsson, V., 1999, Interleukin-1beta activates a short STAT-3 isoform in clonal insulin-secreting cells. FEBS Lett. 442, 57–60.

    PubMed  CAS  Google Scholar 

  • Muller, S., Berger, M., Lehembre, F., Seeler, J. S., Haupt, Y. and Dejean, A., 2000, c-Jun and p53 activity is modulated by SUMO-1 modification. J. Biol. Chem. 275, 13321–13329.

    PubMed  CAS  Google Scholar 

  • Muller, S., Ledl, A. and Schmidt, D., 2004, SUMO: a regulator of gene expression and genome integrity. Oncogene 23, 1998–2008.

    PubMed  Google Scholar 

  • Muromoto, R., Ishida, M., Sugiyama, K., Sekine, Y., Oritani, K., Shimoda, K. and Matsuda, T., 2006, Sumoylation of Daxx regulates IFN-induced growth suppression of B lymphocytes and the hormone receptor-mediated transactivation. J. Immunol. 177, 1160–1170.

    PubMed  CAS  Google Scholar 

  • Navarro-Gonzalez, J. F. and Mora-Fernandez, C., 2008, The role of inflammatory cytokines in diabetic nephropathy. J. Am. Soc. Nephrol. 19, 433–442.

    PubMed  CAS  Google Scholar 

  • Noso, S., Fujisawa, T., Kawabata, Y., Asano, K., Hiromine, Y., Fukai, A., Ogihara, T. and Ikegami, H., 2007, Association of small ubiquitin-like modifier 4 (SUMO4) variant, located in IDDM5 locus, with type 2 diabetes in the Japanese population. J. Clin. Endocrinol. Metab. 92, 2358–2362.

    PubMed  CAS  Google Scholar 

  • Noso, S., Ikegami, H., Fujisawa, T., Kawabata, Y., Asano, K., Hiromine, Y., Sugihara, S., Lee, I., Kawasaki, E., Awata, T. and Ogihara, T., 2006, Association of SUMO4, as a candidate gene for IDDM5, with susceptibility to type 1 diabetes in Asian populations. Ann. N. Y. Acad. Sci. 1079, 41–46.

    PubMed  CAS  Google Scholar 

  • Noso, S., Ikegami, H., Fujisawa, T., Kawabata, Y., Asano, K., Hiromine, Y., Tsurumaru, M., Sugihara, S., Lee, I., Kawasaki, E., Awata, T. and Ogihara, T., 2005, Genetic heterogeneity in association of the SUMO4 M55V variant with susceptibility to type 1 diabetes. Diabetes 54, 3582–3586.

    PubMed  CAS  Google Scholar 

  • O’Sullivan, B., Thompson, A. and Thomas, R., 2007, NF-kappa B as a therapeutic target in autoimmune disease. Expert. Opin. Ther. Targets. 11, 111–122.

    PubMed  Google Scholar 

  • Ochoa, O., Torres, F. M. and Shireman, P. K., 2007, Chemokines and diabetic wound healing. Vascular 15, 350–355.

    PubMed  Google Scholar 

  • Ohly, P., Dohle, C., Abel, J., Seissler, J. and Gleichmann, H., 2000, Zinc sulphate induces metallothionein in pancreatic islets of mice and protects against diabetes induced by multiple low doses of streptozotocin. Diabetologia 43, 1020–1030.

    PubMed  CAS  Google Scholar 

  • Okamoto, T., 2006, NF-kappaB and rheumatic diseases. Endocr. Metab. Immune. Disord. Drug Targets 6, 359–372.

    PubMed  CAS  Google Scholar 

  • Onengut-Gumuscu, S. and Concannon, P., 2002, Mapping genes for autoimmunity in humans: type 1 diabetes as a model. Immunol. Rev. 190, 182–194.

    PubMed  CAS  Google Scholar 

  • Ortis, F., Pirot, P., Naamane, N., Kreins, A. Y., Rasschaert, J., Moore, F., Theatre, E., Verhaeghe, C., Magnusson, N. E., Chariot, A., Orntoft, T. F. and Eizirik, D. L., 2008, Induction of nuclear factor-kappaB and its downstream genes by TNF-alpha and IL-1beta has a pro-apoptotic role in pancreatic beta cells. Diabetologia 51, 1213–1225.

    PubMed  CAS  Google Scholar 

  • Otto-Buczkowska, E., Kazibutowska, Z., Soltyk, J. and Machnica, L., 2008, [Neuropathy and type 1 diabetes mellitus]. Endokrynol. Diabetol. Chor. Przemiany. Materii. Wieku. Rozw. 14, 109–116.

    Google Scholar 

  • Owerbach, D., Pina, L. and Gabbay, K. H., 2004, A 212-kb region on chromosome 6q25 containing the TAB2 gene is associated with susceptibility to type 1 diabetes. Diabetes 53, 1890–1893.

    PubMed  CAS  Google Scholar 

  • Palvimo, J. J., 2007, PIAS proteins as regulators of small ubiquitin-related modifier (SUMO) modifications and transcription. Biochem. Soc. Trans. 35, 1405–1408.

    PubMed  CAS  Google Scholar 

  • Park, Y., Park, S., Kang, J., Yang, S. and Kim, D., 2005, Assessing the validity of the association between the SUMO4 M55V variant and risk of type 1 diabetes. Nat. Genet. 37, 112–113.

    PubMed  CAS  Google Scholar 

  • Pavlovic, D., Andersen, N. A., Mandrup-Poulsen, T. and Eizirik, D. L., 2000, Activation of extracellular signal-regulated kinase (ERK)1/2 contributes to cytokine-induced apoptosis in purified rat pancreatic beta-cells. Eur. Cytokine Netw. 11, 267–274.

    PubMed  CAS  Google Scholar 

  • Peng, S. L., 2008, Transcription factors in autoimmune diseases. Front Biosci. 13, 4218–4240.

    PubMed  CAS  Google Scholar 

  • Pociot, F. and McDermott, M. F., 2002, Genetics of type 1 diabetes mellitus. Genes Immun. 3, 235–249.

    PubMed  CAS  Google Scholar 

  • Poligone, B., Weaver, D. J., Jr., Sen, P., Baldwin, A. S., Jr. and Tisch, R., 2002, Elevated NF-kappaB activation in nonobese diabetic mouse dendritic cells results in enhanced APC function. J. Immunol. 168, 188–196.

    PubMed  CAS  Google Scholar 

  • Powell, J. D., Lerner, C. G., Ewoldt, G. R. and Schwartz, R. H., 1999, The -180 site of the IL-2 promoter is the target of CREB/CREM binding in T cell anergy. J. Immunol. 163, 6631–6639.

    PubMed  CAS  Google Scholar 

  • Pugliese, A. and Eisenbarth, G. S., 2004, Type 1 diabetes mellitus of man: genetic susceptibility and resistance. Adv. Exp. Med. Biol. 552, 170–203.

    PubMed  CAS  Google Scholar 

  • Pugliese, A., Gianani, R., Moromisato, R., Awdeh, Z. L., Alper, C. A., Erlich, H. A., Jackson, R. A. and Eisenbarth, G. S., 1995, HLA-DQB1*0602 is associated with dominant protection from diabetes even among islet cell antibody-positive first-degree relatives of patients with IDDM. Diabetes 44, 608–613.

    PubMed  CAS  Google Scholar 

  • Qu, H., Bharaj, B., Liu, X. Q., Curtis, J. A., Newhook, L. A., Paterson, A. D., Hudson, T. J. and Polychronakos, C., 2005, Assessing the validity of the association between the SUMO4 M55V variant and risk of type 1 diabetes. Nat. Genet. 37, 111–112.

    PubMed  CAS  Google Scholar 

  • Quan, N., Ho, E., La, W., Tsai, Y. H. and Bray, T., 2001, Administration of NF-kappaB decoy inhibits pancreatic activation of NF-kappaB and prevents diabetogenesis by alloxan in mice. FASEB J. 15, 1616–1618.

    PubMed  CAS  Google Scholar 

  • Rabinovitch, A. and Suarez-Pinzon, W. L., 2007, Roles of cytokines in the pathogenesis and therapy of type 1 diabetes. Cell Biochem. Biophys. 48, 159–163.

    PubMed  CAS  Google Scholar 

  • Rapoport, M. J., Mor, A., Vardi, P., Ramot, Y., Winker, R., Hindi, A. and Bistritzer, T., 1998, Decreased secretion of Th2 cytokines precedes Up-regulated and delayed secretion of Th1 cytokines in activated peripheral blood mononuclear cells from patients with insulin-dependent diabetes mellitus. J. Autoimmun. 11, 635–642.

    PubMed  CAS  Google Scholar 

  • Rasschaert, J., Ladriere, 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 RNA+ interferon-gamma-induced apoptosis in primary pancreatic beta-cells. J. Biol. Chem. 280, 33984–33991.

    PubMed  CAS  Google Scholar 

  • Rincon, M., Whitmarsh, A., Yang, D. D., Weiss, L., Derijard, B., Jayaraj, P., Davis, R. J. and Flavell, R. A., 1998, The JNK pathway regulates the in vivo deletion of immature CD4(+)CD8(+) thymocytes. J. Exp. Med. 188, 1817–1830.

    PubMed  CAS  Google Scholar 

  • Rogers, R. S., Horvath, C. M. and Matunis, M. J., 2003, SUMO modification of STAT1 and its role in PIAS-mediated inhibition of gene activation. J. Biol. Chem. 278, 30091–30097.

    PubMed  CAS  Google Scholar 

  • Salinas, S., Briancon-Marjollet, A., Bossis, G., Lopez, M. A., Piechaczyk, M., Jariel-Encontre, I., Debant, A. and Hipskind, R. A., 2004, SUMOylation regulates nucleo-cytoplasmic shuttling of Elk-1. J. Cell Biol. 165, 767–773.

    PubMed  CAS  Google Scholar 

  • Scherbaum, W. A., 1992, Etiology and pathogenesis of type 1 diabetes. Horm. Metab. Res. Suppl. 26, 111–116.

    PubMed  CAS  Google Scholar 

  • Schindler, C., 1999, Cytokines and JAK-STAT signaling. Exp. Cell Res. 253, 7–14.

    PubMed  CAS  Google Scholar 

  • Schindler, C., Levy, D. E. and Decker, T., 2007, JAK-STAT signaling: from interferons to cytokines. J. Biol.Chem. 282, 20059–20063.

    PubMed  CAS  Google Scholar 

  • Schmidt, D. and Muller, S., 2002, Members of the PIAS family act as SUMO ligases for c-Jun and p53 and repress p53 activity. Proc. Natl. Acad. Sci. U.S.A. 99, 2872–2877.

    PubMed  CAS  Google Scholar 

  • Schott-Ohly, P., Lgssiar, A., Partke, H. J., Hassan, M., Friesen, N. and Gleichmann, H., 2004, Prevention of spontaneous and experimentally induced diabetes in mice with zinc sulfate-enriched drinking water is associated with activation and reduction of NF-kappa B and AP-1 in islets, respectively. Exp. Biol. Med. 229, 1177–1185.

    CAS  Google Scholar 

  • Sedimbi, S. K., Luo, X. R., Sanjeevi, C. B., Lernmark, A., Landin-Olsson, M., Arnqvist, H., Bjorck, E., Nystrom, L., Ohlson, L. O., Schersten, B., Ostman, J., Aili, M., Baath, L. E., Carlsson, E., Edenwall, H., Forsander, G., Granstrom, B. W., Gustavsson, I., Hanas, R., Hellenberg, L., Hellgren, H., Holmberg, E., Hornell, H., Ivarsson, S. A., Johansson, C., Jonsell, G., Kockum, K., Lindblad, B., Lindh, A., Ludvigsson, J., Myrdal, U., Neiderud, J., Segnestam, K., Sjoblad, S., Skogsberg, L., Stromberg, L., Stahle, U., Thalme, B., Tullus, K., Tuvemo, T., Wallensteen, M., Westphal, O., Dahlquist, G. and Aman, J., 2007, SUMO4 M55V polymorphism affects susceptibility to type I diabetes in HLA DR3- and DR4-positive Swedish patients. Genes Immun. 8, 518–521.

    PubMed  CAS  Google Scholar 

  • Sen, P., Bhattacharyya, S., Wallet, M., Wong, C. P., Poligone, B., Sen, M., Baldwin, A. S., Jr. and Tisch, R., 2003, NF-kappa B hyperactivation has differential effects on the APC function of nonobese diabetic mouse macrophages. J. Immunol. 170, 1770–1780.

    PubMed  CAS  Google Scholar 

  • Shao, R., Rung, E., Weijdegard, B. and Billig, H., 2006, Induction of apoptosis increases SUMO-1 protein expression and conjugation in mouse periovulatory granulosa cells in vitro. Mol. Reprod. Dev. 73, 50–60.

    PubMed  CAS  Google Scholar 

  • Shaulian, E. and Karin, M., 2002, AP-1 as a regulator of cell life and death. Nat. Cell Biol. 4, E131–E136.

    PubMed  CAS  Google Scholar 

  • She, J. X., 1996, Susceptibility to type I diabetes: HLA-DQ and DR revisited. Immunol. Today 17, 323–329.

    PubMed  CAS  Google Scholar 

  • She, J. X. and Marron, M. P., 1998, Genetic susceptibility factors in type 1 diabetes: linkage, disequilibrium and functional analyses. Curr. Opin. Immunol. 10, 682–689.

    PubMed  CAS  Google Scholar 

  • Shibata, H., 2005, [Regulation of insulin sensitivity by subcellular GLUT4 targeting]. Rinsho Byori. 53, 942–949.

    PubMed  CAS  Google Scholar 

  • Shuai, K. and Liu, B., 2005, Regulation of gene-activation pathways by PIAS proteins in the immune system. Nat. Rev. Immunol. 5, 593–605.

    PubMed  CAS  Google Scholar 

  • Smyth, D. J., Howson, J. M., Lowe, C. E., Walker, N. M., Lam, A. C., Nutland, S., Hutchings, J., Tuomilehto-Wolf, E., Tuomilehto, J., Guja, C., Ionescu-Tirgoviste, C., Undlien, D. E., Ronningen, K. S., Savage, D., Dunger, D. B., Twells, R. C., McArdle, W. L., Strachan, D. P. and Todd, J. A., 2005, Assessing the validity of the association between the SUMO4 M55V variant and risk of type 1 diabetes. Nat. Genet. 37, 110–111.

    PubMed  CAS  Google Scholar 

  • Strickland, F. M. and Richardson, B. C., 2008, Epigenetics in human autoimmunity. Epigenetics in autoimmunity – DNA methylation in systemic lupus erythematosus and beyond. Autoimmunity 41, 278–286.

    PubMed  CAS  Google Scholar 

  • Studholme, S., 2008, Diabetic retinopathy. J. Perioper. Pract. 18, 205–210.

    PubMed  Google Scholar 

  • Su, B., Jacinto, E., Hibi, M., Kallunki, T., Karin, M. and Ben-Neriah, Y., 1994, JNK is involved in signal integration during costimulation of T lymphocytes. Cell 77, 727–736.

    PubMed  Google Scholar 

  • Suarez-Pinzon, W. L. and Rabinovitch, A., 2001, Approaches to type 1 diabetes prevention by intervention in cytokine immunoregulatory circuits. Int. J. Exp. Diabetes Res. 2, 3–17.

    PubMed  CAS  Google Scholar 

  • Takasu, N., Asawa, T., Komiya, I., Nagasawa, Y. and Yamada, T., 1991a, Alloxan-induced DNA strand breaks in pancreatic islets. Evidence for H2O2 as an intermediate. J. Biol. Chem. 266, 2112–2114.

    PubMed  CAS  Google Scholar 

  • Takasu, N., Komiya, I., Asawa, T., Nagasawa, Y. and Yamada, T., 1991b, Streptozocin- and alloxan-induced H2O2 generation and DNA fragmentation in pancreatic islets. H2O2 as mediator for DNA fragmentation. Diabetes 40, 1141–1145.

    PubMed  CAS  Google Scholar 

  • Tiedge, M., Lortz, S., Drinkgern, J. and Lenzen, S., 1997, Relation between antioxidant enzyme gene expression and antioxidative defense status of insulin-producing cells. Diabetes 46, 1733–1742.

    PubMed  CAS  Google Scholar 

  • Tost, J., 2009, DNA methylation: an introduction to the biology and the disease-associated changes of a promising biomarker. Methods Mol. Biol. 507, 3–20.

    PubMed  CAS  Google Scholar 

  • Trajkovski, M., Mziaut, H., Altkruger, A., Ouwendijk, J., Knoch, K. P., Muller, S. and Solimena, M., 2004, Nuclear translocation of an ICA512 cytosolic fragment couples granule exocytosis and insulin expression in {beta}-cells. J. Cell Biol. 167, 1063–1074.

    PubMed  CAS  Google Scholar 

  • Tran, P. O., Parker, S. M., LeRoy, E., Franklin, C. C., Kavanagh, T. J., Zhang, T., Zhou, H., Vliet, P., Oseid, E., Harmon, J. S. and Robertson, R. P., 2004, Adenoviral overexpression of the glutamylcysteine ligase catalytic subunit protects pancreatic islets against oxidative stress. J. Biol. Chem. 279, 53988–53993.

    PubMed  CAS  Google Scholar 

  • Tsurumaru, M., Kawasaki, E., Ida, H., Migita, K., Moriuchi, A., Fukushima, K., Fukushima, T., Abiru, N., Yamasaki, H., Noso, S., Ikegami, H., Awata, T., Sasaki, H. and Eguchi, K., 2006, Evidence for the role of small ubiquitin-like modifier 4 as a general autoimmunity locus in the Japanese population. J. Clin. Endocrinol. Metab. 91, 3138–3143.

    PubMed  CAS  Google Scholar 

  • Ungureanu, D., Vanhatupa, S., Kotaja, N., Yang, J., Aittomaki, S., Janne, O. A., Palvimo, J. J. and Silvennoinen, O., 2003, PIAS proteins promote SUMO-1 conjugation to STAT1. Blood 102, 3311–3313.

    PubMed  CAS  Google Scholar 

  • van der, Werf N., Kroese, F. G., Rozing, J. and Hillebrands, J. L., 2007, Viral infections as potential triggers of type 1 diabetes. Diabetes Metab. Res. Rev. 23, 169–183.

    PubMed  Google Scholar 

  • von Herrath, M. G., 2004, Pathogenesis of type 1 diabetes: a viewpoint. Adv. Exp. Med. Biol. 552, 317–321.

    Google Scholar 

  • voodi-Semiromi, A., Laloraya, M., Kumar, G. P., Purohit, S., Jha, R. K. and She, J. X., 2004, A mutant Stat5b with weaker DNA binding affinity defines a key defective pathway in nonobese diabetic mice. J. Biol. Chem. 279, 11553–11561.

    Google Scholar 

  • Wang, C. Y., Podolsky, R. and She, J. X., 2006, Genetic and functional evidence supporting SUMO4 as a type 1 diabetes susceptibility gene. Ann. N. Y. Acad. Sci. 1079, 257–267.

    PubMed  CAS  Google Scholar 

  • Wang, C. Y. and She, J. X., 2008, SUMO4 and its role in type 1 diabetes pathogenesis. Diabetes Metab. Res. Rev. 24, 93–102.

    PubMed  CAS  Google Scholar 

  • Wang, C. Y., Yang, P. and She, J. X., 2005, Assessing the validity of the association between the SUMO4 M55V variant and risk of type 1 diabetes. Nat. Genet. 37, 112–113.

    CAS  Google Scholar 

  • Weaver, D. J., Jr., Poligone, B., Bui, T., bdel-Motal, U. M., Baldwin, A. S., Jr. and Tisch, R., 2001, Dendritic cells from nonobese diabetic mice exhibit a defect in NF-kappa B regulation due to a hyperactive I kappa B kinase. J. Immunol. 167, 1461–1468.

    PubMed  CAS  Google Scholar 

  • Wei, W., Yang, P., Pang, J., Zhang, S., Wang, Y., Wang, M. H., Dong, Z., She, J. X. and Wang, C. Y., 2008, A stress-dependent SUMO4 sumoylation of its substrate proteins. Biochem. Biophys. Res. Commun. 375, 454–459.

    PubMed  CAS  Google Scholar 

  • Westwick, J. K., Weitzel, C., Minden, A., Karin, M. and Brenner, D. A., 1994, Tumor necrosis factor alpha stimulates AP-1 activity through prolonged activation of the c-Jun kinase. J. Biol. Chem. 269, 26396–26401.

    PubMed  CAS  Google Scholar 

  • Williams, M. S. and Kwon, J., 2004, T cell receptor stimulation, reactive oxygen species, and cell signaling. Free Radic. Biol. Med. 37, 1144–1151.

    PubMed  CAS  Google Scholar 

  • Wilson, A. G., 2008, Epigenetic regulation of gene expression in the inflammatory response and relevance to common diseases. J. Periodontol. 79, 1514–1519.

    PubMed  CAS  Google Scholar 

  • Wotton, D., Higgins, J. A., O'Hehir, R. E., Lamb, J. R. and Lake, R. A., 1995, Differential induction of the NF-AT complex during restimulation and the induction of T-cell anergy. Hum. Immunol. 42, 95–102.

    PubMed  CAS  Google Scholar 

  • Yamashina, K., Yamamoto, H., Chayama, K., Nakajima, K. and Kikuchi, A., 2006, Suppression of STAT3 activity by Duplin, which is a negative regulator of the Wnt signal. J. Biochem. 139, 305–314.

    PubMed  CAS  Google Scholar 

  • Yang, P., Li, M., Guo, D., Gong, F., Adam, B. L., Atkinson, M. and Wang, C. Y., 2008, Comparative analysis of the islet proteome between NOD/Lt and ALR/Lt mice. Ann. N. Y. Acad. Sci. 1150, 68–71.

    Google Scholar 

  • Yoo, Y. J., Gao, G. and Zhang, K., 2007, Case-control association analysis of rheumatoid arthritis with candidate genes using related cases. BMC. Proc. 1 (Suppl 1), S33.

    PubMed  Google Scholar 

  • Yoon, J. W. and Jun, H. S., 2005, Autoimmune destruction of pancreatic beta cells. Am. J. Ther. 12, 580–591.

    PubMed  Google Scholar 

  • Zhou, W., Ryan, J. J. and Zhou, H., 2004, Global analyses of sumoylated proteins in Saccharomyces cerevisiae. Induction of protein sumoylation by cellular stresses. J. Biol. Chem. 279, 32262–32268.

    PubMed  CAS  Google Scholar 

  • Zhoucun, A., Zhang, S. and Xiao, C., 2001, Preliminary studies on associations of IDDM3, IDDM4, IDDM5 and IDDM8 with IDDM in Chengdu population. Chin. Med. Sci. J. 16, 120–122.

    PubMed  CAS  Google Scholar 

  • Ziegler, A. G. and Standl, E., 1994, [Type-1 diabetes: the pathogenesis of an immune disease]. Dtsch. Med. Wochenschr. 119, 705–706.

    PubMed  CAS  Google Scholar 

  • Zingarelli, B., 2005, Nuclear factor-kappaB. Crit. Care Med. 33, S414–S416.

    PubMed  Google Scholar 

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Acknowledgements

Our research is supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the Juvenile Diabetes Research Foundation International (JDRFI) and the American Diabetes Association (ADA), and by the Bridge Funding from Tongji Hospital of HUST to CYW. The authors declare that they have no competing financial interest.

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Authors and Affiliations

  1. The Center for Biotechnology and Genomic Medicine, Medical College of Georgia, 30912, Augusta, GA, USA

    Jixin Zhong & Ping Yang

  2. The Center for Biomedical Research, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, China

    Jixin Zhong, Ping Yang & Cong-Yi Wang

  3. Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, China

    Jixin Zhong & Feili Gong

  4. The Center for Biotechnology and Genomic Medicine, Medical College of Georgia, 30912, 1120 15th Street, Augusta, GA, USA

    Cong-Yi Wang

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Zhong, J., Yang, P., Gong, F., Wang, CY. (2009). SUMO4-Encoded Genetic Susceptibility to Type 1 Diabetes. In: Wilson, V. (eds) SUMO Regulation of Cellular Processes. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-2649-1_16

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