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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 and Vihinen, Mauno LU , et al. (2000) In Journal of Biological Chemistry 275(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. me 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... (More)
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. me 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. (Less)
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type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
275
issue
22
pages
16802 - 16809
publisher
ASBMB
external identifiers
  • wos:000087392200058
  • scopus:0038824426
ISSN
1083-351X
DOI
10.1074/jbc.M908944199
language
English
LU publication?
no
id
91d6e244-8ff4-4b05-8108-d0750f90275b (old id 3852045)
date added to LUP
2013-06-28 15:30:04
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2017-06-11 03:33:14
@article{91d6e244-8ff4-4b05-8108-d0750f90275b,
  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. me 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.},
  author       = {Pitkanen, J and Doucas, V and Sternsdorf, T and Nakajima, T and Aratani, S and Jensen, K and Will, H and Vahamurto, P and Ollila, J and Vihinen, Mauno and Scott, HS and Antonarakis, SE and Kudoh, J and Shimizu, N and Krohn, K and Peterson, P},
  issn         = {1083-351X},
  language     = {eng},
  number       = {22},
  pages        = {16802--16809},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {The autoimmune regulator protein has transcriptional transactivating properties and interacts with the common coactivator CREB-binding protein},
  url          = {http://dx.doi.org/10.1074/jbc.M908944199},
  volume       = {275},
  year         = {2000},
}