The autoimmune regulator (AIRE) is a DNA-binding protein

The autoimmune regulator (AIRE) protein is a putative transcription regulat or with two plant homeodomain-type zinc fingers, a putative DNA-binding dom ain (SAND), and four nuclear receptor binding LXXLL motifs. We have shown h ere that in vitro, recombinant AIRE can form homodimers and homotetramers t hat were also detected in thymic protein extracts. Recombinant AIRE also ol igomerizes spontaneously upon phosphorylation by CAMP dependent protein kin ase A or protein kinase C. Similarly, thymic AIRE protein is phosphorylated at the tyrosine and serine/threonine residues. AIRE dimers and tetramers, but not the monomers, can bind to G-doublets with the ATTGGTTA motif and th e TTATTA-box. Competition assays revealed that sequences with one TTATTA mo tif and two tandem repeats of ATTGGTTA had the highest binding affinity. Th ese findings demonstrate that AIRE is an important DNA binding molecule inv olved in immune regulation.