title: The autoimmune regulator (AIRE) is a DNA-binding protein.
abstract: The autoimmune regulator (AIRE) protein is a putative transcription regulator with two plant homeodomain-type zinc fingers, a putative DNA-binding domain (SAND), and four nuclear receptor binding LXXLL motifs. We have shown here that in vitro, recombinant AIRE can form homodimers and homotetramers that were also detected in thymic protein extracts. Recombinant AIRE also oligomerizes spontaneously upon phosphorylation by cAMP dependent protein kinase 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 the TTATTA-box. Competition assays revealed that sequences with one TTATTA motif and two tandem repeats of ATTGGTTA had the highest binding affinity. These findings demonstrate that AIRE is an important DNA binding molecule involved in immune regulation.
authors.affiliation: Department of Pathology, Immunology, and Laboratory Medicine, Center for Mammalian Genetics and Diabetes Center of Excellence, College of Medicine, University of Florida, Gainesville, Florida 32610, USA.
authors.forename: P G
authors.initials: PG
authors.lastname: Kumar
authors.forename: M
authors.initials: M
authors.lastname: Laloraya
authors.forename: C Y
authors.initials: CY
authors.lastname: Wang
authors.forename: Q G
authors.initials: QG
authors.lastname: Ruan
authors.forename: A
authors.initials: A
authors.lastname: Davoodi-Semiromi
authors.forename: K J
authors.initials: KJ
authors.lastname: Kao
authors.forename: J X
authors.initials: JX
authors.lastname: She
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010766:Phosphorylation; D017510:Protein Folding; D017386:Sequence Homology, Amino Acid; D013950:Thymus Gland / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D016335:Zinc Fingers; D000096927:AIRE Protein
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; D014157:Transcription Factors; D000096927:AIRE Protein