title: The biophysical and biochemical properties of the autoimmune regulator (AIRE) protein.
abstract: AIRE (for autoimmune regulator) is a multidomain protein that performs a fundamental function in the thymus and possibly in the secondary lymphoid organs: the regulation, especially in the sense of activation, of the process of gene transcription in cell lines deputed to the presentation of self-antigens to the maturing T lymphocytes. The apoptosis of the elements bearing T-cell receptors with critical affinity for the exhibited self-antigens prevents the escape of autoreactive clones and represents a simple and efficient mechanism of deletional self-tolerance. However, AIRE action relies on an articulated complex of biophysical and biochemical properties, in most cases attributable to single subspecialized domains. Here a thorough review of the matter is presented, with a privileged look at the pathogenic changes of AIRE that interfere with such properties and lead to the impairment in its chief function.
authors.affiliation: Department of Pediatrics - Neonatal Intensive Care, V. Fazzi Regional Hospital, Piazza F. Muratore, I-73100, Lecce, Italy. Electronic address: rperniola@hotmail.com.
authors.forename: Roberto
authors.initials: R
authors.lastname: Perniola
authors.affiliation: Biomolecular NMR Laboratory, Center of Translational Genomics and Bioinformatics, Dulbecco Telethon Institute at San Raffaele Scientific Institute, Via Olgettina 58, I-20132, Milan, Italy. Electronic address: musco.giovanna@hsr.it.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Musco
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D011485:Protein Binding; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000096927:AIRE Protein
chemical_list: D014157:Transcription Factors; D000096927:AIRE Protein
keywords: 100-kDa speckled protein; 110-kDa speckled protein; 140-kDa speckled protein; AIRE; APECED; APS1; Autoimmune polyendocrinopathies; CARD; CBP; CIITA; CREB-binding protein; ChIP; DAXX; Deaf1; EMSA; GST; Gfp; HEK293; HSR; ING2; MHCII; MHCII transactivator; MM/PBSA; MS; Molecular Mechanics/Poisson–Boltzmann Surface Area; NB; NLS; NMR; NucP41/75; P-TEFb; PGE; PHD; PIAS1; PK; PML; PRR; PTM; Post-translational protein processing; Protein conformation; RING; RNA-PolII; RNA-polymerase II; SAND; STAT; Self-tolerance; Sp100; Sp100, AIRE, NucP41/75 and Deaf1; Sp110; Sp140; Transcription factors; TsAg; aa; amino acid(s); autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy; autoimmune polyglandular syndrome type 1; autoimmune regulator; caspase-recruitment domain; chromatin immunoprecipitation; class-II major histocompatibility complex; coIP; coimmunoprecipitation; death-associated protein 6; deformed epidermal autoregulatory factor 1; electrophoretic mobility shift assay; glutathione-S-transferase; green fluorescent protein; homogeneously-staining region; human-embryonic-kidney epithelial-cell line 293; inhibitor of growth 2; mTEC; mass spectrometry; medullary thymic epithelial cell; nuclear body; nuclear localization signal; nuclear magnetic resonance; nuclear phosphoprotein 41/75; plant homeodomain; positive transcription elongation factor b; post-translational modification; proline-rich region; promiscuous gene expression; promyelocytic leukemia; protein inhibitor of activated STAT 1; protein kinase; really-interesting new gene; signal transducer and activator of transcription; tissue-specific antigen