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Title

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

Authors
Pitkanen, J.
Doucas, V.
Sternsdorf, T.
Nakajima, T.
Aratani, S.
Jensen, K.
Will, H.
Vahamurto, P.
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Published in Journal of Biological Chemistry. 2000, vol. 275, no. 22, p. 16802-16809
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 NH(2)-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.
Keywords Amino Acid SequenceAnimalsCREB-Binding ProteinCell LineDimerizationHumansMolecular Sequence DataMutagenesis, Site-DirectedNuclear Proteins/ metabolismProtein BindingSequence Homology, Amino AcidTrans-Activators/ metabolismTranscription Factors/chemistry/ metabolismTranscription, GeneticTranscriptional ActivationTwo-Hybrid System Techniques
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PMID: 10748110
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Other version: http://www.jbc.org/content/275/22/16802.full.pdf
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PITKANEN, J. et al. 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, n° 22, p. 16802-16809. https://archive-ouverte.unige.ch/unige:8968

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Deposited on : 2010-07-12

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