The biophysical and biochemical properties of the autoimmune regulator (AIRE) protein

• Published in: Biochimica et biophysica acta Vol. 1842; no. 2; pp. 326 - 337
• Main Authors: Perniola, Roberto, Musco, Giovanna
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-02-2014
• Subjects: AIRE Protein; Animals; Autoimmune polyendocrinopathies; Gene Expression Regulation; Humans; Models, Molecular; Mutation; Post-translational protein processing; Protein Binding; Protein conformation; Protein Multimerization; Protein Structure, Tertiary; Self-tolerance; Transcription factors; Transcription Factors - chemistry; Transcription Factors - genetics; Transcription Factors - metabolism; Post-translational protein processing; CIITA; TsAg; Transcription factors; AIRE; Deaf1; Protein conformation; PTM; Autoimmune polyendocrinopathies; Self-tolerance; ChIP; PHD; CARD; P-TEFb; CBP; Gfp; PRR; Sp100; HEK293; ING2; NLS; Sp140; EMSA; RING; mTEC; APECED; aa; DAXX; SAND; RNA-PolII; HSR; MS; GST; PML; MM/PBSA; PGE; PIAS1; NMR; STAT; APS1; NB; MHCII; Sp110; PK; coIP; NucP41/75; promiscuous gene expression; Molecular Mechanics/Poisson–Boltzmann Surface Area; 140-kDa speckled protein; CREB-binding protein; RNA-polymerase II; death-associated protein 6; plant homeodomain; autoimmune regulator; green fluorescent protein; class-II major histocompatibility complex; nuclear body; MHCII transactivator; medullary thymic epithelial cell; autoimmune polyglandular syndrome type 1; inhibitor of growth 2; glutathione-S-transferase; deformed epidermal autoregulatory factor 1; 100-kDa speckled protein; nuclear localization signal; signal transducer and activator of transcription; homogeneously-staining region; protein kinase; chromatin immunoprecipitation; autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy; electrophoretic mobility shift assay; 110-kDa speckled protein; mass spectrometry; protein inhibitor of activated STAT 1; nuclear phosphoprotein 41/75; tissue-specific antigen; positive transcription elongation factor b; human-embryonic-kidney epithelial-cell line 293; amino acid(s); post-translational modification; proline-rich region; nuclear magnetic resonance; Sp100, AIRE, NucP41/75 and Deaf1; caspase-recruitment domain; promyelocytic leukemia; really-interesting new gene; coimmunoprecipitation
• ISSN: 0925-4439; 0006-3002; 1879-260X
• DOI: 10.1016/j.bbadis.2013.11.020

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.
•Chief function of AIRE is the regulation of gene transcription in the thymus.•The amino terminus of AIRE drives its homomerization, nuclear import and localization.•PHD1 recognizes the unmethylated tail of histone H3 and targets AIRE-dependent genes.•PHD2 is thought to play a critical role in the activation of gene transcription.•The identification of AIRE partners represents a new exciting vein of research.