The autoimmune regulator protein has transcriptional transactivating properties and interacts with the common coactivator CREB-binding protein

Jukka Pitkänen, Vassilis Doucas, Thomas Sternsdorf, Toshihiro Nakajima, Satoko Aratani, Kirsten Jensen, Hans Will, Perttu Vähämurto, Juha Ollila, Mauno Vihinen, Hamish S. Scott, Stylianos E. Antonarakis, Jun Kudoh, Nobuyoshi Shimizu, Kai Krohn, Pärt Peterson

研究成果: Article査読

193 被引用数 (Scopus)

抄録

Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy, caused by mutations in the autoimmune regulator (AIRE) gene, is an autosomal recessive autoimmune disease characterized by the breakdown of tolerance to organ-specific antigens. The 545 amino acid protein encoded by AIRE contains several structural motifs suggestive of a transcriptional regulator and bears similarity to cellular proteins involved in transcriptional control. We show here that AIRE fused to a heterologous DNA binding domain activates transcription from a reporter promoter, and the activation seen requires the full-length protein or more than one activation domain. At the structural level AIRE forms homodimers through the NH2-terminal domain, and molecular modeling for this domain suggests a four-helix bundle structure. In agreement, we show that the common transcriptional coactivator CREB-binding protein (CBP) interacts with AIRE in vitro and in yeast nuclei through the CH1 and CH3 conserved domains. We suggest that the transcriptional transactivation properties of AIRE together with its interaction with CBP might be important in its function as disease-causing mutations almost totally abolish the activation effect.

本文言語English
ページ(範囲)16802-16809
ページ数8
ジャーナルJournal of Biological Chemistry
275
22
DOI
出版ステータスPublished - 2000 6月 2
外部発表はい

ASJC Scopus subject areas

  • 生化学
  • 分子生物学
  • 細胞生物学

フィンガープリント

「The autoimmune regulator protein has transcriptional transactivating properties and interacts with the common coactivator CREB-binding protein」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル