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 Kudo, Nobuyoshi Shimizu, Kai Krohn, Pärt Peterson

Research output: Contribution to journalArticle

188 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)16802-16809
Number of pages8
JournalJournal of Biological Chemistry
Volume275
Issue number22
DOIs
Publication statusPublished - 2000 Jun 2

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CREB-Binding Protein
Chemical activation
Autoimmune Polyendocrinopathies
Mutation
Proteins
Molecular modeling
Transcription
Regulator Genes
Yeast
Transcriptional Activation
Autoimmune Diseases
Genes
Yeasts
Antigens
Amino Acids
DNA

ASJC Scopus subject areas

  • Biochemistry

Cite this

The autoimmune regulator protein has transcriptional transactivating properties and interacts with the common coactivator CREB-binding protein. / Pitkänen, Jukka; Doucas, Vassilis; Sternsdorf, Thomas; Nakajima, Toshihiro; Aratani, Satoko; Jensen, Kirsten; Will, Hans; Vähämurto, Perttu; Ollila, Juha; Vihinen, Mauno; Scott, Hamish S.; Antonarakis, Stylianos E.; Kudo, Jun; Shimizu, Nobuyoshi; Krohn, Kai; Peterson, Pärt.

In: Journal of Biological Chemistry, Vol. 275, No. 22, 02.06.2000, p. 16802-16809.

Research output: Contribution to journalArticle

Pitkänen, J, Doucas, V, Sternsdorf, T, Nakajima, T, Aratani, S, Jensen, K, Will, H, Vähämurto, P, Ollila, J, Vihinen, M, Scott, HS, Antonarakis, SE, Kudo, J, Shimizu, N, Krohn, K & Peterson, P 2000, 'The autoimmune regulator protein has transcriptional transactivating properties and interacts with the common coactivator CREB-binding protein', Journal of Biological Chemistry, vol. 275, no. 22, pp. 16802-16809. https://doi.org/10.1074/jbc.M908944199
Pitkänen, Jukka ; Doucas, Vassilis ; Sternsdorf, Thomas ; Nakajima, Toshihiro ; Aratani, Satoko ; Jensen, Kirsten ; Will, Hans ; Vähämurto, Perttu ; Ollila, Juha ; Vihinen, Mauno ; Scott, Hamish S. ; Antonarakis, Stylianos E. ; Kudo, Jun ; Shimizu, Nobuyoshi ; Krohn, Kai ; Peterson, Pärt. / The autoimmune regulator protein has transcriptional transactivating properties and interacts with the common coactivator CREB-binding protein. In: Journal of Biological Chemistry. 2000 ; Vol. 275, No. 22. pp. 16802-16809.
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