Role of PHD fingers and COOH-terminal 30 amino acids in AIRE transactivation activity.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomic autoimmune disease resulting from the defective function of a gene codifying for a transcription factor named autoimmune regulation (AIRE). The AIRE protein contains several domains among which two PHD fingers involved in the transcriptional activation. We investigated the function of the two PHD finger domains and the COOH terminal portion of AIRE by using several mutated constructs transfected in mammalian cells and a luciferase reporter assay. The results predict that the second PHD as well as the COOH terminal regions have marked transactivational properties. The COOH terminal region contains the fourth LXXLL and the PXXPXP motifs which play a critical role in mediating the transactivation capacity of the AIRE protein. Our study provides a definition of the role of the PHD fingers in transactivation and identifies a new transactivation domain of the AIRE protein localized in the COOH terminal region.