DAXX is a new AIRE interacting protein.

The AIRE protein plays a remarkable role as a regulator of the central tolerance by controlling the promiscuous expression of tissue-specific Ags (TSAs) in thymic medullary epithelial cells (mTECs). Defects in the AIRE gene cause the Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), a rare disease frequent in Iranian Jews, Finns and Sardinian population. To this day, the precise function of AIRE protein in regulating transcription and its interacting proteins are still 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 yeast two hybrid system to identify AIRE interacting proteins. The Yeast Two Hybrid 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.