Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/53860
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Type: Journal article
Title: AIRE'S CARD revealed, a new structure for the central tolerance provokes transcriptional plasticity
Author: Ferguson, B.
Alexander, C.
Rossi, S.
Liiv, I.
Rebane, A.
Worth, C.
Wong, J.
Laan, M.
Peterson, P.
Jenkinson, E.
Anderson, G.
Scott, H.
Cooke, A.
Rich, T.
Citation: Journal of Biological Chemistry, 2008; 283(3):1723-1731
Publisher: Amer Soc Biochemistry Molecular Biology Inc
Issue Date: 2008
ISSN: 0021-9258
1083-351X
Statement of
Responsibility: 
Brian J. Ferguson, Clare Alexander, Simona W. Rossi, Ingrid Liiv, Ana Rebane, Catherine L. Worth, Joyce Wong, Martti Laan, Pärt Peterson, Eric J. Jenkinson, Graham Anderson, Hamish S. Scott, Anne Cooke and Tina Rich
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.
Keywords: Thymus Gland
Hela Cells
Cell Nucleus
Animals
Humans
Mice
Transcription Factors
Immune Tolerance
Transcription, Genetic
Amino Acid Sequence
Protein Structure, Tertiary
Protein Transport
Mutation
Models, Biological
Models, Molecular
Software
Molecular Sequence Data
Cyclic AMP Response Element-Binding Protein
Receptor Activator of Nuclear Factor-kappa B
Transcriptional Activation
DOI: 10.1074/jbc.M707211200
Appears in Collections:Aurora harvest 5
Medicine publications

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