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

Pitkanen, J.; Doucas, V.; Sternsdorf, T.; Nakajima, T.; Aratani, S.; Jensen, K.; Will, H.; Vahamurto, P.; Ollila, J.; Vihinen, M.; Scott, Hamish Steele; Antonarakis, Stylianos; Kudoh, J.; Shimizu, N.; Krohn, K.; Peterson, P.

doi:10.1074/jbc.M908944199

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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. Ollila, J. Vihinen, M. Scott, Hamish Steele Antonarakis, Stylianos Kudoh, J. Shimizu, N. Krohn, K. Peterson, P. show all authors [1 - 16]
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 Sequence — Animals — CREB-Binding Protein — Cell Line — Dimerization — Humans — Molecular Sequence Data — Mutagenesis, Site-Directed — Nuclear Proteins/ metabolism — Protein Binding — Sequence Homology, Amino Acid — Trans-Activators/ metabolism — Transcription Factors/chemistry/ metabolism — Transcription, Genetic — Transcriptional Activation — Two-Hybrid System Techniques
Identifiers		DOI: 10.1074/jbc.M908944199 PMID: 10748110
Full text		Article - Limited access to UNIGE Other version: http://www.jbc.org/content/275/22/16802.full.pdf
Structures		Faculté de médecine / Section de médecine clinique / Département de médecine
Citation (ISO format)		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. doi: 10.1074/jbc.M908944199 https://archive-ouverte.unige.ch/unige:8968