Autoimmune regulator: From loss of function to autoimmunity

Genes and Immunity

Volumn 4, Issue 1, 2003, Pages 12-21

  Pitkanen J ^a   Peterson, Part ^a  

^a UNIVERSITY OF TAMPERE   (Finland)

Author keywords

[No Author keywords available]

Indexed keywords

AUTOIMMUNE REGULATOR PROTEIN; BINDING PROTEIN; CELL NUCLEUS RECEPTOR; CYCLIC AMP RESPONSIVE ELEMENT BINDING PROTEIN BINDING PROTEIN; DNA BINDING PROTEIN; REGULATOR PROTEIN; TRANSCRIPTION FACTOR; UNCLASSIFIED DRUG; ZINC FINGER PROTEIN; TRANSACTIVATOR PROTEIN;

ADDISON DISEASE; AMINO TERMINAL SEQUENCE; AUTOIMMUNE DISEASE; AUTOIMMUNE POLYENDOCRINOPATHY CANDIDIASIS ECTODERMAL DYSTROPHY; AUTOIMMUNITY; DENDRITE; DNA BINDING MOTIF; ENDOCRINE DISEASE; EPITHELIUM CELL; FETUS LIVER; GENE MUTATION; HUMAN; HYPOPARATHYROIDISM; IMMUNOLOGICAL TOLERANCE; INSULIN DEPENDENT DIABETES MELLITUS; LIVER CELL; LYMPH NODE CELL; MONOCYTE; NONHUMAN; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN MOTIF; REGULATOR GENE; REVIEW; SPLEEN CELL; THYMOCYTE; TRANSCRIPTION REGULATION; ANIMAL; BIOSYNTHESIS; GENETICS; IMMUNOLOGY; METABOLISM; PHYSIOLOGY;

ANIMALS; AUTOIMMUNE DISEASES; HUMANS; TRANS-ACTIVATORS; TRANSCRIPTION FACTORS;

EID: 0037790522     PISSN: 14664879     EISSN: None     Source Type: Journal    
DOI: 10.1038/sj.gene.6363929     Document Type: Review

References (98)

1. Neufeld M, Maclaren N, Blizzard R. Autoimmune polyglandular syndromes. Pediatr Ann 1980; 9: 154-162.
2. Perheentupa J. Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). Horm Metab Res 1996; 28: 353-356.
3. Ahonen P, Myllarniemi S, Sipila I, Perheentupa J. Clinical variation of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) in a series of 68 patients. N Engl J Med 1990; 322: 1829-1836.
4. Krohn K, Uibo R, Aavik E, Peterson P, Savilahti K. Identification by molecular cloning of an autoantigen associated with Addison's disease as steroid 17 alpha-hydroxylase. Lancet 1992; 339: 770-773.
5. Uibo R, Aavik E, Peterson P et al. Autoantibodies to cytochrome P450 enzymes P450scc, P450c17, and P450c21 in autoimmune polyglandular disease types I and II and in isolated Addison's disease. J Clin Endocrinol Metab 1994; 78: 323-328.
6. Winqvist O, Karlsson FA, Kampe O. 21-Hydroxylase, a major autoantigen in idiopathic Addison's disease. Lancet 1992; 339: 1559-1562.
7. Winqvist O, Gustafsson J, Rorsman F, Karlsson FA, Kampe O. Two different cytochrome P450 enzymes are the adrenal antigens in autoimmune polyendocrine syndrome type I and Addison's disease. J Clin Invest 1993; 92: 2377-2385.
8. Betterle C, Dal Pra C, Mantero F, Zanchetta R. Autoimmune adrenal insufficiency and autoimmune polyendocrine syndromes: autoantibodies, autoantigens, and their applicability in diagnosis and disease prediction. Endocr Rev 2002; 23: 327-364.
9. Zlotogora J, Shapiro MS. Polyglandular autoimmune syndrome type I among Iranian Jews. J Med Genet 1992; 29: 824-826.
10. Rosatelli MC, Meloni A, Devoto M et al. A common mutation in Sardinian autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy patients. Hum Genet 1998; 103: 428-434.
11. The Finnish-German APECED Consortium. An autoimmune disease, APECED, caused by mutations in a novel gene featuring two PHD-type zinc-finger domains. Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. Nat Genet 1997; 17: 399-403.
12. Nagamine K, Peterson P, Scott HS et al. Positional cloning of the APECED gene. Nat Genet 1997; 17: 393-398.
13. Mittaz L, Rossier C, Heino M et al. Isolation and characterization of the mouse Aire gene. Biochem Biophys Res Commun 1999; 255: 483-490.
14. Sternsdorf T, Grotzinger T, Jensen K, Will H. Nuclear dots: actors on many stages. Immunobiology 1997; 198: 307-331.
15. Sternsdorf T, Jensen K, Reich B, Will H. The nuclear dot protein sp100, characterization of domains necessary for dimerization, subcellular localization and modification by small ubiquitin-like modifiers. J Biol Chem 1999; 274: 12 555-12 566.
16. Guldner HH, Szostecki C, Schroder P et al. Splice variants of the nuclear dot-associated Sp100 protein contain homologies to HMG-1 and a human nuclear phosphoprotein-box motif. J Cell Sci 1999; 112: 733-747.
17. Zuklys S, Balciunaite G, Agarwal A et al. Normal thymic architecture and negative selection are associated with Aire expression, the gene defective in the autoimmune-polyendo-crinopathy-candidiasis-ectodermal dystrophy (APECED). J Immunol 2000; 165: 1976-1983.
18. Heino M, Peterson P, Kudoh J et al. Autoimmune regulator is expressed in the cells regulating immune tolerance in thymus medulla. Biochem Biophys Res Commun 1999; 257: 821-825.
19. Heino M, Peterson P, Sillanpää N et al. RNA and protein expression of the murine autoimmune regulator gene (Aire) in normal, RelB-deficient and in NOD mouse. Eur J Immunol 2000; 30: 1884-1893.
20. Kogawa K, Nagafuchi S, Katsuta H et al. Expression of AIRE gene in peripheral monocyte/dendritic cell lineage. Immunol Lett 2002; 80: 195-198.
21. Halonen M, Pelto-Huikko M, Eskelin P, et al. Subcellular location and expression pattern of autoimmune regulator (Aire), the mouse orthologue for human gene defective in autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED). J Histochem Cytochem 2001; 49: 197-208.
22. Blechschmidt K, Schweiger M, Wertz K et al. The mouse Aire gene: comparative genomic sequencing, gene organization, and expression. Genome Res 1999; 9: 158-166.
23. Backstrom BT, Muller U, Hausmann B, Palmer E. Positive selection through a motif in the alphabeta T cell receptor. Science 1998; 281: 835-838.
24. Wang B, Levelt C, Salio M et al. Over-expression of CD3 epsilon transgenes blocks T lymphocyte development. Int Immunol 1995; 7: 435-448.
25. Nabarra B, Andrianarison I. Thymus reticulum of autoimmune mice 3. Ultrastructural study of NOD (non-obese diabetic) mouse thymus. Int J Exp Pathol 1991; 72: 275-287.
26. Atlan-Gepner C, Naspetti M, Valero R et al. Disorganization of thymic medulla precedes evolution towards diabetes in female NOD mice. Autoimmunity 1999; 31: 249-260.
27. Wang CY, Davoodi-Semiromi A, Huang W et al. Characterization of mutations in patients with autoimmune polyglandular syndrome type 1 (APS1). Hum Genet 1998; 103: 681-685.
28. Pearce SH, Cheetham T, Imrie H et al. A common and recurrent 13-bp deletion in the autoimmune regulator gene in British kindreds with autoimmune polyendocrinopathy type 1. Am J Hum Genet 1998; 63: 1675-1684.
29. Scott HS, Heino M, Peterson P et al. Common mutations in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy patients of different origins. Mol Endocrinol 1998; 12: 1112-1119.
30. Myhre AG, Björses P, Dalen A, Husebye ES. Three sisters with Addison's disease. J Clin Endocrinol Metab 1998; 83: 4204-4206.
31. Ward L, Paquette J, Seidman, E et al. Severe autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy in an adolescent girl with a novel AIRE mutation: response to immunosuppressive therapy. J Clin Endocrinol Metab 1999; 84: 844-852.
32. Heino M, Scott HS, Chen Q et al. Mutation analyses of North American APS-1 patients. Hum Mutat 1999; 13: 69-74.
33. Björses P, Halonen M, Palvimo JJ et al. Mutations in the AIRE gene: effects on subcellular location and transactivation function of the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy protein. Am J Hum Genet 2000; 66: 378-392.
34. Ishii T, Suzuki Y, Ando N, Matsuo N, Ogata T. Novel mutations of the autoimmune regulator gene in two siblings with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. J Clin Endocrinol Metab 2000; 85: 2922-2926.
35. Cihakova D, Trebusak K, Heino M et al. Novel AIRE mutations and P450 cytochrome autoantibodies in Central and Eastern European patients with APECED. Hum Mutat 2001; 18: 225-232.
36. Myhre AG, Halonen M, Eskelin P et al. Autoimmune polyendocrine syndrome type 1 (APS I) in Norway. Clin Endocrinol (Oxf) 2001; 54: : 211-217.
37. Saugier-Veber P, Drouot N, Wolf LM et al. Identification of a novel mutation in the autoimmune regulator (AIRE-1) gene in a French family with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. Eur J Endocrinol 2001; 144: 347-351.
38. Soderbergh A, Rorsman F, Halonen M et al. Autoantibodies against aromatic L-amino acid decarboxylase identifies a subgroup of patients with Addison's disease. J Clin Endocrinol Metab 2000; 85: 460-463.
39. Cetani F, Barbesino G, Borsari S et al. A novel mutation of the autoimmune regulator gene in an Italian kindred with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy, acting in a dominant fashion and strongly cosegregating with hypothyroid autoimmune thyroiditis. J Clin Endocrinol Metab 2001; 86: 4747-4752.
40. Heino M, Peterson P, Kudoh, J et al. APECED mutations in the autoimmune regulator (AIRE) gene. Hum Mutat 2001; 18: 205-211.
41. Meloni A, Perniola R, Faa V et al. Delineation of the molecular defects in the AIRE gene in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy patients from Southern Italy. J Clin Endocrinol Metab 2002; 87: 841-846.
42. Halonen M, Eskelin P, Myhre AG et al. AIRE mutations and human leukocyte antigen genotypes as determinants of the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy phenotype. J Clin Endocrinol Metab 2002; 87: 2568-2574.
43. Gylling M, Tuomi T, Biorses P et al. ss-cell autoantibodies, human leukocyte antigen II alleles, and type 1 diabetes in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. J Clin Endocrinol Metab 2000; 85: 4434-4440.
44. Meyer G, Donner H, Herwig J et al. Screening for an AIRE-1 mutation in patients with Addison's disease type 1 diabetes Graves' disease and Hashimoto's thyroiditis as well as in APECED syndrome. Clin Endocrinol (Oxf) 2001; 54: 335-338.
45. Nithiyananthan R, Heward JM, Allahabadia A et al. A heterozygous deletion of the autoimmune regulator (AIRE1) gene autoimmune thyroid disease, and type 1 diabetes: no evidence for association. J Clin Endocrinol Metab 2000; 85: 1320-1322.
46. Vaidya B, Imrie H, Geatch DR et al. Association analysis of the cytotoxic T lymphocyte antigen-4 (CTLA-4) and autoimmune regulator-1 (AIRE-1) genes in sporadic autoimmune Addison's disease. J Clin Endocrinol Metab 2000; 85: 688-691.
47. Pitkänen J, Vähämurto P, Krohn K, Peterson P. Subcellular localization of the autommume regulator protein: characterization of nuclear targeting and transcriptional activation domain. J Biol Chem 2001; 276: 19 597-19 602.
48. Björses P, Pelto-Huikko M, Kaukonen J et al. Localization of the APECED protein in distinct nuclear structures. Hum Mol Genet 1999; 8: 259-266.
49. Rinderle C, Christensen HM, Schweiger S, Lehrach H, Yaspo ML. AIRE encodes a nuclear protein co-localizing with cytoskeletal filaments: altered sub-cellular distribution of mutants lacking the PHD zinc fingers. Hum Mol Genet 1999; 8: 277-290.
50. Doucas V, Evans RM. The PML nuclear compartment and cancer. Biochim Biophys Acta 1996; 1288: M25-M29.
51. Nishi K, Yoshida M, Fujiwara D et al. Leptomycin B targets a regulatory cascade of crm1, a fission yeast nuclear protein, involved in control of higher order chromosome structure and gene expression. J Biol Chem 1994; 269: 6320-6324.
52. Fukuda M, Asano S, Nakamura T et al. CRM1 is responsible for intracellular transport mediated by the nuclear export signal. Nature 1997; 390: 308-311.
53. Kudo N, Matsumori N, Taoka H et al. Leptomycin B inactivates CRM1/exportin 1 by covalent modification at a cysteine residue in the central conserved region. Proc Natl Acad Sci USA 1999; 96: 9112-9117.
54. Nakielny S, Dreyfuss G. Nuclear export of proteins and RNAs. Curr Opin Cell Biol 1997; 9: 420-429.
55. Komeili A, O'Shea EK. Nuclear transport and transcription. Curr Opin Cell Biol 2000; 12: 355-360.
56. Rodriguez JA, Henderson BR. Identification of a functional nuclear export sequence in BRCA1. J Biol Chem 2000; 275: 38 589-38 596.
57. Baumann CT, Maruvada P, Hager GL, Yen PM. Nuclear cytoplasmic shuttling by thyroid hormone receptors: multiple protein interactions are required for nuclear retention. J Biol Chem 2001; 276: 11 237-11 245.
58. Taagepera S, McDonald D, Loeb JE et al. Nuclear-cytoplasmic shuttling of C-ABL tyrosine kinase. Proc Natl Acad Sci USA 1998; 95: 7457-7462.
59. Stommel JM, Marchenko ND, Jimenez GS et al. A leucine-rich nuclear export signal in the p53 tetramerization domain: regulation of subcellular localization and p53 activity by NES masking. EMBO J 1999; 18: 1660-1672.
60. Kim SS, Chen YM, O'Leary E et al. A novel member of the RING finger family, KRIP-1, associates with the KRAB-A transcriptional repressor domain of zinc finger proteins. Proc Natl Acad Sci LISA 1996; 93: 15 299-15 304.
61. Ge Q, Nilasena DS, O'Brien CA, Frank MB, Targoff IN. Molecular analysis of a major antigenic region of the 240-kD protein of Mi-2 autoantigen. J Clin Invest 1995; 96: 1730-1737.
62. Gibbons RJ, Bachoo S, Picketts DJ et al. Mutations in transcriptional regulator ATRX establish the functional significance of a PHD-like domain. Nat Genet 1997; 17: 146-148.
63. Thenot S, Bonnet S, Boulahtouf A et al. Effect of ligand and DNA binding on the interaction between human transcription intermediary factor 1alpha and estrogen receptors. Mol Endocrinol 1999; 13: 2137-2150.
64. Yano T, Nakamura T, Blechman J et al. Nuclear punctate distribution of ALL-1 is conferred by distinct elements at the N terminus of the protein. Proc Natl Acad Sci USA 1997; 94: 7286-7291.
65. Gibson TJ, Ramu C, Gemund C, Aasland R. The APECED polyglandular autoimmune syndrome protein, AIRE-1, contains the SAND domain and is probably a transcription factor. Trends Biochem Sci 1998; 23: 242-244.
66. Pitkanen J, Doucas V, Sternsdorf T et al. The autoimmune regulator protein has transcriptional transactivating properties and interacts with the common coactivator CREB-binding protein. J Biol Chem 2000; 275: 16 802-16 809.
67. Lamond AI, Earnshaw WC. Structure and function in the nucleus. Science 1998; 280: 547-553.
68. Janknecht R, Hunter T. Versatile molecular glue. Transcriptional control. Curr Biol 1996; 6: 951-954.
69. Kamei Y, Xu L, Heinzel T et al. A CBP integrator complex mediates transcriptional activation and AP-1 inhibition by nuclear receptors. Cell 1996; 85: 403-414.
70. Goldman PS, Tran VK, Goodman RH. The multifunctional role of the co-activator CBP in transcriptional regulation. Recent Prog Horm Res 1997; 52: 103-119.
71. Chakravarti D, LaMorte VJ, Nelson MC et al. Role of CBP/P300 in nuclear receptor signalling. Nature 1996; 383: 99-103.
72. Heery DM, Kalkhoven E, Hoare S, Parker MG. A signature motif in transcriptional co-activators mediates binding to nuclear receptors. Nature 1997; 387: 733-736.
73. Bhattacharya S, Eckner R, Grossman S et al. Cooperation of Stat2 and p300/CBP in signalling induced by interferon-alpha. Nature 1996; 383: 344-347.
74. Arany Z, Huang LE, Eckner R et al. An essential role for p300/CBP in the cellular response to hypoxia. Proc Natl Acad Sci USA 1996; 93: 12 969-12 973.
75. Lundblad JR, Kwok RP, Laurance ME, Harter ML, Goodman RH. Adenoviral E1A-associated protein p300 as a functional homologue of the transcriptional co-activator CBP. Nature 1995; 374: 85-88.
76. Yang XJ, Ogryzko VV, Nishikawa J, Howard BH, Nakatani Y. A p300/CBP-associated factor that competes with the adenoviral oncoprotein E1A. Nature 1996; 382: 319-324.
77. Chen H, Lin RJ, Schiltz RL et al. Nuclear, receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300. Cell 1997; 90: 569-580.
78. Voegel JJ, Heine MJ, Tini M et al. The coactivator TIF2 contains three nuclear receptor-binding motifs and mediates transactivation. through CBP binding-dependent and -independent pathways. Embo J 1998; 17: 507-519.
79. Ogryzko VV, Schiltz RL, Russanova V, Howard BH, Nakatani Y. The transcriptional coactivators p300 and CBP are histone acetyltransferases. Cell 1996; 87: 953-959.
80. Bannister AJ, Kouzarides T. The CBP co-activator is a histone acetyltransferase. Nature 1996; 384: 641-643.
81. Doucas V, Tini M, Egan DA, Evans RM. Modulation of CREB binding protein function by the promyelocytic (PML) oncoprotein suggests a role for nuclear bodies in hormone signaling. Proc Natl Acad Sci USA 1999; 96: 2627-2632.
82. Chan HM, La Thangue NB. p300/CBP proteins: HATs for transcriptional bridges and scaffolds. J Cell Sci 2001; 114: 2363-2373.
83. Huggenvik JI, Michelson RJ, Collard MW et al. Characterization of a nuclear deformed epidermal autoregulatory factor-1 (DEAF-1)-related (NUDR) transcriptional regulator protein. Mol Endocrinol 1998; 12: 1619-1639.
84. Bottomley MJ, Collard MW, Huggenvik JI et al. The SAND domain structure defines a novel DNA-binding fold in transcriptional regulation. Nat Struct Biol 2001; 8: 626-633.
85. Kumar PG, Laloraya M, Wang CY et al. The autoimmune regulator (AIRE) is a DNA-binding protein. J Biol Chem 2001; 276: 41 357-41 364.
86. Derbinski J, Schulte A, Kyewski B, Klein L. Promiscuous gene expression in medullary thymic epithelial cells mirrors the peripheral self. Nat Immunol 2001; 2: 1032-1039.
87. Kyewski B, Derbinski J, Gotter J, Klein L. Promiscuous gene expression and central T-cell tolerance: more than meets the eye. Trends Immunol 2002; 23: 364-371.
88. Pietropaolo M, Giannoukakis N, Trucco M. Cellular environment and freedom of gene expression. Nat Immunol 2002; 3: 335; discussion 336.
89. Pugliese A, Diez J. Lymphoid organs contain diverse cells expressing self-molecules. Nat Immunol 2002; 3: 335-336; discussion 336.
90. Kishimoto H, Sprent J. The thymus and negative selection. Immunol Res 2000; 21: 315-323.
91. Page DM. Cutting edge: thymic selection and autoreactivity are regulated by multiple coreceptors involved in T cell activation. J Immunol 1999; 163: 3577-3581.
92. Grewal IS, Flavell RA. CD40 and CD154 in cell-mediated immunity. Annu Rev Immunol 1998; 16: 111-135.
93. Amakawa R, Hakem A, Kundig TM et al. Impaired negative selection of T cells in Hodgkin's disease antigen CD30-deficient mice. Cell 1996; 84: 551-562.
94. Romagnani P, Annunziato F, Manetti R et al. High CD30 ligand expression by epithelial cells and Hassal's corpuscles in the medulla of human thymus. Blood 1998; 91: 3323-3332.
95. Annunziato F, Romagnani P, Cosmi L, Lazzeri E, Romagnani S. Chemokines and lymphopoiesis in human thymus. Trends Immunol 2001; 22: 277-281.
96. Sakaguchi S. Policing the regulators. Nat Immunol 2001; 2: 283-284.
97. Ramsey C, Winqvist O, Puhakka L et al. Aire deficient mice develop multiple features of APECED phenotype and show altered immune response. Hum Mol Genet 2002; 11: 397-409.
98. Kyewski B, Derbinski J, Gotter J, Klein L. Promiscuous gene expression and central T-cell tolerance: more than meets the eye. Trends Immunol 2002; 23: 364-371.