AIRE Functions As an E3 Ubiquitin Ligase

DOI PDF 被引用文献4件
  • Daisuke Uchida
    1Division of Molecular Immunology, Institute for Enzyme Research, University of Tokushima, Tokushima 770-8503, Japan
  • Shigetsugu Hatakeyama
    2Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan
  • Akemi Matsushima
    1Division of Molecular Immunology, Institute for Enzyme Research, University of Tokushima, Tokushima 770-8503, Japan
  • Hongwei Han
    1Division of Molecular Immunology, Institute for Enzyme Research, University of Tokushima, Tokushima 770-8503, Japan
  • Satoshi Ishido
    4Division of Microbiology, Department of Genome Sciences, Kobe University Graduate School of Medicine, Hyogo 650-0017, Japan
  • Hak Hotta
    4Division of Microbiology, Department of Genome Sciences, Kobe University Graduate School of Medicine, Hyogo 650-0017, Japan
  • Jun Kudoh
    5Department of Molecular Biology, Keio University School of Medicine, Tokyo 160-8582, Japan
  • Nobuyoshi Shimizu
    5Department of Molecular Biology, Keio University School of Medicine, Tokyo 160-8582, Japan
  • Vassilis Doucas
    6Département Biologie des Genomes, Institut Jacques Monod, 75251 Paris, France
  • Keiichi I. Nakayama
    2Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan
  • Noriyuki Kuroda
    1Division of Molecular Immunology, Institute for Enzyme Research, University of Tokushima, Tokushima 770-8503, Japan
  • Mitsuru Matsumoto
    1Division of Molecular Immunology, Institute for Enzyme Research, University of Tokushima, Tokushima 770-8503, Japan

抄録

<jats:p>Autoimmune regulator (AIRE) gene mutation is responsible for the development of autoimmune-polyendocrinopathy-candidiasis ectodermal dystrophy, an organ-specific autoimmune disease with monogenic autosomal recessive inheritance. AIRE is predominantly expressed in medullary epithelial cells of the thymus and is considered to play important roles in the establishment of self-tolerance. AIRE contains two plant homeodomain (PHD) domains, and the novel role of PHD as an E3 ubiquitin (Ub) ligase has just emerged. Here we show that the first PHD (PHD1) of AIRE mediates E3 ligase activity. The significance of this finding was underscored by the fact that disease-causing missense mutations in the PHD1 (C311Y and P326Q) abolished its E3 ligase activity. These results add a novel enzymatic function for AIRE and suggest an indispensable role of the Ub proteasome pathway in the establishment of self-tolerance, in which AIRE is involved.</jats:p>

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