DAXX is a new AIRE-interacting protein.
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 the AIRE gene cause the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy, a rare disease frequent in Iranian Jews, Finns, and Sardinian population. To this day, the precise function of the AIRE protein in regulating transcription and its interacting proteins has yet to be entirely clarified. The knowledge of novel AIRE interactors and their precise role will improve our knowledge of its biological activity and address some of the foremost autoimmunity-related questions. In this study, we have used a yeast two-hybrid system to identify AIRE-interacting proteins. This approach led us to the discovery of a new AIRE-interacting protein called DAXX. The protein is known to be a multifunctional adaptor with functions both in apoptosis and in transcription regulation pathways. The interaction between AIRE and DAXX has been validated by in vivo coimmunoprecipitation analysis and colocalization study in mammalian cells. The interaction has been further confirmed by showing in transactivation assays that DAXX exerts a strong repressive role on the transcriptional activity of AIRE.
Meloni
Alessandra
A
Istituto di Neurogenetica e Neurofarmacologia, Consiglio Nazionale delle Ricerche, Università degli Studi di Cagliari, 09121 Cagliari, Italy.
Meloni
Allesandra
A
Fiorillo
Edoardo
E
Corda
Denise
D
Incani
Federica
F
Serra
Maria Luisa
ML
Contini
Antonella
A
Cao
Antonio
A
Rosatelli
Maria Cristina
MC
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D019556:COS Cells; D002522:Chlorocebus aethiops; D056970:Co-Repressor Proteins; D030342:Genetic Diseases, Inborn / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D018832:Molecular Chaperones; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016884:Polyendocrinopathies, Autoimmune; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics / Q000276:immunology; D020798:Two-Hybrid System Techniques; D000096927:AIRE Protein
D048868:Adaptor Proteins, Signal Transducing; D056970:Co-Repressor Proteins; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D000096927:AIRE Protein; C106985:DAXX protein, human