title: AIRE acetylation and deacetylation: effect on protein stability and transactivation activity.
abstract: BACKGROUND
  The AIRE protein plays a remarkable role as a regulator of central tolerance by controlling the promiscuous expression of tissue-specific antigens in thymic medullary epithelial cells. Defects in AIRE gene cause the autoimmune polyendocrinopathy- candidiasis-ectodermal dystrophy, a rare disease frequent in Iranian Jews, Finns, and Sardinian population.
  
  
  RESULTS
  In this study, we have precisely mapped, by mass spectrometry experiments, the sites of protein acetylation and, by mutagenesis assays, we have described a set of acetylated lysines as being crucial in influencing the subcellular localization of AIRE. Furthermore, we have also determined that the de-acetyltransferase enzymes HDAC1-2 are involved in the lysine de-acetylation of AIRE.
  
  
  CONCLUSIONS
  On the basis of our results and those reported in literature, we propose a model in which lysines acetylation increases the stability of AIRE in the nucleus. In addition, we observed that the interaction of AIRE with deacetylases complexes inhibits its transcriptional activity and is probably responsible for the instability of AIRE, which becomes more susceptible to degradation in the proteasome.
authors.forename: Federica
authors.initials: F
authors.lastname: Incani
authors.forename: Maria
authors.initials: M
authors.lastname: Serra
authors.forename: Alessandra
authors.initials: A
authors.lastname: Meloni
authors.forename: Carla
authors.initials: C
authors.lastname: Cossu
authors.forename: Luisella
authors.initials: L
authors.lastname: Saba
authors.forename: Tiziana
authors.initials: T
authors.lastname: Cabras
authors.forename: Irene
authors.initials: I
authors.lastname: Messana
authors.forename: Maria C
authors.initials: MC
authors.lastname: Rosatelli
mesh_terms: D000107:Acetylation; D000818:Animals; D019556:COS Cells; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D002522:Chlorocebus aethiops; D056284:Histone Deacetylase 1 / Q000235:genetics / Q000378:metabolism; D056464:Histone Deacetylase 2 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D013058:Mass Spectrometry; D008954:Models, Biological; D055550:Protein Stability; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*; D015533:Transcriptional Activation / Q000502:physiology*; D050880:p300-CBP Transcription Factors / Q000235:genetics / Q000378:metabolism; D000096927:AIRE Protein; D000099224:p300-CBP-Associated Factor
chemical_list: D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000096927:AIRE Protein; D000099224:p300-CBP-Associated Factor; C110550:HDAC1 protein, human; C533423:HDAC2 protein, human