2004年1月
AIRE functions as an E3 ubiquitin ligase
JOURNAL OF EXPERIMENTAL MEDICINE
- 巻
- 199
- 号
- 2
- 開始ページ
- 167
- 終了ページ
- 172
- 記述言語
- 英語
- 掲載種別
- DOI
- 10.1084/jem.20031291
- 出版者・発行元
- ROCKEFELLER UNIV PRESS
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 in 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 PHD 1 (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.
- リンク情報
- ID情報
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- DOI : 10.1084/jem.20031291
- ISSN : 0022-1007
- Web of Science ID : WOS:000188369700003