The Full Wiki

Autoimmune regulator: Wikis

Advertisements

Note: Many of our articles have direct quotes from sources you can cite, within the Wikipedia article! This article doesn't yet, but we're working on it! See more info or our list of citable articles.

Encyclopedia

From Wikipedia, the free encyclopedia

edit
Autoimmune regulator (autoimmune polyendocrinopathy candidiasis ectodermal dystrophy)

PDB rendering based on 1xwh.
Available structures
1xwh
Identifiers
Symbols AIRE; AIRE1; APECED; APS1; APSI; PGA1
External IDs OMIM607358 MGI1338803 HomoloGene327 GeneCards: AIRE Gene
RNA expression pattern
PBB GE AIRE 208090 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 326 11634
Ensembl ENSG00000160224 ENSMUSG00000000731
UniProt O43918 Q3ZB65
RefSeq (mRNA) NM_000383 NM_009646
RefSeq (protein) NP_000374 NP_033776
Location (UCSC) Chr 21:
44.53 - 44.54 Mb
Chr 10:
77.43 - 77.45 Mb
PubMed search [2] [3]

The Autoimmune Regulator, abbreviated AIRE, is a human transcription factor expressed in the medulla of the thymus and is important in the prevention of autoimmune disease.

Contents

Function

In the thymus it causes transcription of a wide selection of organ-specific genes which create proteins that are usually only expressed in peripheral tissues, creating an "immunological self-shadow" in the thymus.[1][2] It is important that self-reactive T cells which bind strongly to self-antigen are eliminated in the thymus (via the process of negative selection), otherwise they can later bind to their corresponding self-proteins and create an autoimmune reaction. So the expression of non-local proteins by AIRE reduces the threat of autoimmunity occurring later on by allowing for the elimination of auto-reactive T cells which bind antigens not traditionally found in the thymus.

Research on the knockout mouse has demonstrated that Aire functions through initiating the transcription of a diverse set of self-antigens, such as insulin, in the thymus.[3] This expression then allows maturing thymocytes to become tolerant towards peripheral organs, thereby suppressing autoimmune disease.[4]

The AIRE gene is expressed in many other tissues as well.[5]

Pathology

It is mutated in the rare autoimmune syndrome Autoimmune Polyendocrinopathy Syndrome type 1 (APS-1), also known as Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED). Disruption of AIRE results in the development of a range of autoimmune diseases, the most common clinical conditions in the syndrome are hypoparathyroidism, primary adrenocortical failure and chronic mucocutaneous candidiasis.[6]

A gene knockout of the murine homolog Aire has created a transgenic mouse model to study the mechanism of disease in human patients.[7]

Interactions

Autoimmune regulator has been shown to interact with CREB binding protein.[8][9]

See also

References

  1. ^ Anderson, M.S. et al. (2002) Projection of an Immunological Self-Shadow Within the Thymus by the Aire Protein. Science 298 (5597), 1395-1401
  2. ^ Liston, A. et al. (2003) Aire regulates negative selection of organ-specific T cells. Nat Immunol 4 (4), 350-354
  3. ^ Anderson MS, Venanzi ES, Klein L, Chen Z, Berzins SP, Turley SJ, von Boehmer H, Bronson R, Dierich A, Benoist C, Mathis D (2002). "Projection of an immunological self shadow within the thymus by the aire protein". Science 298 (5597): 1395–401. doi:10.1126/science.1075958. PMID 12376594.  
  4. ^ Liston A, Lesage S, Wilson J, Peltonen L, Goodnow CC (2003). "Aire regulates negative selection of organ-specific T cells". Nat. Immunol. 4 (4): 350–4. doi:10.1038/ni906. PMID 12612579.  
  5. ^ BioGPS > AIRE > Gene expression/activity chart Retrieved on Dec 19, 2009
  6. ^ OMIM. [1]
  7. ^ Ramsey C, Winqvist O, Puhakka L, Halonen M, Moro A, Kämpe O, Eskelin P, Pelto-Huikko M, Peltonen L (2002). "Aire deficient mice develop multiple features of APECED phenotype and show altered immune response". Hum. Mol. Genet. 11 (4): 397–409. doi:10.1093/hmg/11.4.397. PMID 11854172.  
  8. ^ Pitkänen, J; Doucas V, Sternsdorf T, Nakajima T, Aratani S, Jensen K, Will H, Vähämurto P, Ollila J, Vihinen M, Scott H S, Antonarakis S E, Kudoh J, Shimizu N, Krohn K, Peterson P (Jun. 2000). "The autoimmune regulator protein has transcriptional transactivating properties and interacts with the common coactivator CREB-binding protein". J. Biol. Chem. (UNITED STATES) 275 (22): 16802–9. doi:10.1074/jbc.M908944199. ISSN 0021-9258. PMID 10748110.  
  9. ^ Iioka, Takashi; Furukawa Keizo, Yamaguchi Akira, Shindo Hiroyuki, Yamashita Shunichi, Tsukazaki Tomoo (Aug. 2003). "P300/CBP acts as a coactivator to cartilage homeoprotein-1 (Cart1), paired-like homeoprotein, through acetylation of the conserved lysine residue adjacent to the homeodomain". J. Bone Miner. Res. (United States) 18 (8): 1419–29. ISSN 0884-0431. PMID 12929931.  

Further reading

  • Björses P, Aaltonen J, Horelli-Kuitunen N, et al. (1998). "Gene defect behind APECED: a new clue to autoimmunity.". Hum. Mol. Genet. 7 (10): 1547–53. doi:10.1093/hmg/7.10.1547. PMID 9735375.  
  • Heino M, Peterson P, Kudoh J, et al. (2001). "APECED mutations in the autoimmune regulator (AIRE) gene.". Hum. Mutat. 18 (3): 205–11. doi:10.1002/humu.1176. PMID 11524731.  
  • Sato K, Nakajima K, Imamura H, et al. (2003). "A novel missense mutation of AIRE gene in a patient with autoimmune polyendocrinopathy, candidiasis and ectodermal dystrophy (APECED), accompanied with progressive muscular atrophy: case report and review of the literature in Japan.". Endocr. J. 49 (6): 625–33. doi:10.1507/endocrj.49.625. PMID 12625412.  
  • Ruan QG, She JX (2004). "Autoimmune polyglandular syndrome type 1 and the autoimmune regulator.". Clin. Lab. Med. 24 (1): 305–17. doi:10.1016/j.cll.2004.01.008. PMID 15157567.  
  • Holmdahl R (2007). "Aire-ing self antigen variability and tolerance.". Eur. J. Immunol. 37 (3): 598–601. doi:10.1002/eji.200737152. PMID 17323409.  
  • Aaltonen J, Björses P, Sandkuijl L, et al. (1995). "An autosomal locus causing autoimmune disease: autoimmune polyglandular disease type I assigned to chromosome 21.". Nat. Genet. 8 (1): 83–7. doi:10.1038/ng0994-83. PMID 7987397.  
  • Aaltonen J, Horelli-Kuitunen N, Fan JB, et al. (1997). "High-resolution physical and transcriptional mapping of the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy locus on chromosome 21q22.3 by FISH.". Genome Res. 7 (8): 820–9. PMID 9267805.  
  • Nagamine K, Peterson P, Scott HS, et al. (1997). "Positional cloning of the APECED gene.". Nat. Genet. 17 (4): 393–8. doi:10.1038/ng1297-393. PMID 9398839.  
  • Aaltonen, Johanna (1997). "An autoimmune disease, APECED, caused by mutations in a novel gene featuring two PHD-type zinc-finger domains.". Nat. Genet. 17 (4): 399–403. doi:10.1038/ng1297-399. PMID 9398840.  
  • Scott HS, Heino M, Peterson P, et al. (1998). "Common mutations in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy patients of different origins.". Mol. Endocrinol. 12 (8): 1112–9. doi:10.1210/me.12.8.1112. PMID 9717837.  
  • Heino M, Scott HS, Chen Q, et al. (1999). "Mutation analyses of North American APS-1 patients.". Hum. Mutat. 13 (1): 69–74. doi:10.1002/(SICI)1098-1004(1999)13:1<69::AID-HUMU8>3.0.CO;2-6. PMID 9888391.  
  • Björses P, Pelto-Huikko M, Kaukonen J, et al. (1999). "Localization of the APECED protein in distinct nuclear structures.". Hum. Mol. Genet. 8 (2): 259–66. doi:10.1093/hmg/8.2.259. PMID 9931333.  
  • Rinderle C, Christensen HM, Schweiger S, et al. (1999). "AIRE encodes a nuclear protein co-localizing with cytoskeletal filaments: altered sub-cellular distribution of mutants lacking the PHD zinc fingers.". Hum. Mol. Genet. 8 (2): 277–90. doi:10.1093/hmg/8.2.277. PMID 9931335.  
  • Björses P, Halonen M, Palvimo JJ, et al. (2000). "Mutations in the AIRE gene: effects on subcellular location and transactivation function of the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy protein.". Am. J. Hum. Genet. 66 (2): 378–92. doi:10.1086/302765. PMID 10677297.  
  • Pitkänen J, Doucas V, Sternsdorf T, et al. (2000). "The autoimmune regulator protein has transcriptional transactivating properties and interacts with the common coactivator CREB-binding protein.". J. Biol. Chem. 275 (22): 16802–9. doi:10.1074/jbc.M908944199. PMID 10748110.  
  • Hattori M, Fujiyama A, Taylor TD, et al. (2000). "The DNA sequence of human chromosome 21.". Nature 405 (6784): 311–9. doi:10.1038/35012518. PMID 10830953.  
  • Pitkänen J, Vähämurto P, Krohn K, Peterson P (2001). "Subcellular localization of the autoimmune regulator protein. characterization of nuclear targeting and transcriptional activation domain.". J. Biol. Chem. 276 (22): 19597–602. doi:10.1074/jbc.M008322200. PMID 11274163.  
  • Saugier-Veber P, Drouot N, Wolf LM, et al. (2001). "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. 144 (4): 347–51. doi:10.1530/eje.0.1440347. PMID 11275943.  

External links

Advertisements

Advertisements






Got something to say? Make a comment.
Your name
Your email address
Message