AIRE's CARD Revealed, a New Structure for Central Tolerance Provokes Transcriptional Plasticity

Research output: Contribution to journalArticle

Standard

AIRE's CARD Revealed, a New Structure for Central Tolerance Provokes Transcriptional Plasticity. / Ferguson, BJ; Alexander, C; Rossi, Simona; Liiv, I; Rebane, A; Worth, CL; Wong, J; Laan, M; Peterson, P; Jenkinson, Eric; Anderson, Graham; Scott, HS; Cooke, A; Rich, T.

In: Journal of Biological Chemistry, Vol. 283, No. 3, 16.11.2007, p. 1723-31.

Research output: Contribution to journalArticle

Harvard

Ferguson, BJ, Alexander, C, Rossi, S, Liiv, I, Rebane, A, Worth, CL, Wong, J, Laan, M, Peterson, P, Jenkinson, E, Anderson, G, Scott, HS, Cooke, A & Rich, T 2007, 'AIRE's CARD Revealed, a New Structure for Central Tolerance Provokes Transcriptional Plasticity', Journal of Biological Chemistry, vol. 283, no. 3, pp. 1723-31. https://doi.org/10.1074/jbc.M707211200

APA

Ferguson, BJ., Alexander, C., Rossi, S., Liiv, I., Rebane, A., Worth, CL., Wong, J., Laan, M., Peterson, P., Jenkinson, E., Anderson, G., Scott, HS., Cooke, A., & Rich, T. (2007). AIRE's CARD Revealed, a New Structure for Central Tolerance Provokes Transcriptional Plasticity. Journal of Biological Chemistry, 283(3), 1723-31. https://doi.org/10.1074/jbc.M707211200

Vancouver

Author

Ferguson, BJ ; Alexander, C ; Rossi, Simona ; Liiv, I ; Rebane, A ; Worth, CL ; Wong, J ; Laan, M ; Peterson, P ; Jenkinson, Eric ; Anderson, Graham ; Scott, HS ; Cooke, A ; Rich, T. / AIRE's CARD Revealed, a New Structure for Central Tolerance Provokes Transcriptional Plasticity. In: Journal of Biological Chemistry. 2007 ; Vol. 283, No. 3. pp. 1723-31.

Bibtex

@article{4385ad91a62f4fd5b20d6f80a9beba1d,
title = "AIRE's CARD Revealed, a New Structure for Central Tolerance Provokes Transcriptional Plasticity",
abstract = "Developing T cells encounter peripheral self-antigens in the thymus in order to delete autoreactive clones. It is now known that the autoimmune regulator protein (AIRE), which is expressed in thymic medullary epithelial cells, plays a key role in regulating the thymic transcription of these peripheral tissue-specific antigens. Mutations in the AIRE gene are associated with a severe multiorgan autoimmune syndrome (APECED), and autoimmune reactivities are manifest in AIRE-deficient mice. Functional AIRE protein is expressed as distinct nuclear puncta, although no structural basis existed to explain their relevance to disease. In addressing the cell biologic basis for APECED, we made the unexpected discovery that an AIRE mutation hot spot lies in a caspase recruitment domain. Combined homology modeling and in vitro data now show how APECED mutations influence the activity of this transcriptional regulator. We also provide novel in vivo evidence for AIRE's association with a global transcription cofactor, which may underlie AIRE's focal, genome-wide, alteration of the transcriptome.",
author = "BJ Ferguson and C Alexander and Simona Rossi and I Liiv and A Rebane and CL Worth and J Wong and M Laan and P Peterson and Eric Jenkinson and Graham Anderson and HS Scott and A Cooke and T Rich",
year = "2007",
month = nov,
day = "16",
doi = "10.1074/jbc.M707211200",
language = "English",
volume = "283",
pages = "1723--31",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology",
number = "3",

}

RIS

TY - JOUR

T1 - AIRE's CARD Revealed, a New Structure for Central Tolerance Provokes Transcriptional Plasticity

AU - Ferguson, BJ

AU - Alexander, C

AU - Rossi, Simona

AU - Liiv, I

AU - Rebane, A

AU - Worth, CL

AU - Wong, J

AU - Laan, M

AU - Peterson, P

AU - Jenkinson, Eric

AU - Anderson, Graham

AU - Scott, HS

AU - Cooke, A

AU - Rich, T

PY - 2007/11/16

Y1 - 2007/11/16

N2 - Developing T cells encounter peripheral self-antigens in the thymus in order to delete autoreactive clones. It is now known that the autoimmune regulator protein (AIRE), which is expressed in thymic medullary epithelial cells, plays a key role in regulating the thymic transcription of these peripheral tissue-specific antigens. Mutations in the AIRE gene are associated with a severe multiorgan autoimmune syndrome (APECED), and autoimmune reactivities are manifest in AIRE-deficient mice. Functional AIRE protein is expressed as distinct nuclear puncta, although no structural basis existed to explain their relevance to disease. In addressing the cell biologic basis for APECED, we made the unexpected discovery that an AIRE mutation hot spot lies in a caspase recruitment domain. Combined homology modeling and in vitro data now show how APECED mutations influence the activity of this transcriptional regulator. We also provide novel in vivo evidence for AIRE's association with a global transcription cofactor, which may underlie AIRE's focal, genome-wide, alteration of the transcriptome.

AB - Developing T cells encounter peripheral self-antigens in the thymus in order to delete autoreactive clones. It is now known that the autoimmune regulator protein (AIRE), which is expressed in thymic medullary epithelial cells, plays a key role in regulating the thymic transcription of these peripheral tissue-specific antigens. Mutations in the AIRE gene are associated with a severe multiorgan autoimmune syndrome (APECED), and autoimmune reactivities are manifest in AIRE-deficient mice. Functional AIRE protein is expressed as distinct nuclear puncta, although no structural basis existed to explain their relevance to disease. In addressing the cell biologic basis for APECED, we made the unexpected discovery that an AIRE mutation hot spot lies in a caspase recruitment domain. Combined homology modeling and in vitro data now show how APECED mutations influence the activity of this transcriptional regulator. We also provide novel in vivo evidence for AIRE's association with a global transcription cofactor, which may underlie AIRE's focal, genome-wide, alteration of the transcriptome.

U2 - 10.1074/jbc.M707211200

DO - 10.1074/jbc.M707211200

M3 - Article

C2 - 17974569

VL - 283

SP - 1723

EP - 1731

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 3

ER -