|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
22
|
|
pubmed:dateCreated |
2001-5-30
|
|
pubmed:abstractText |
The autoimmune regulator (AIRE) gene, defective in the hereditary autoimmune disease APECED, encodes a transcriptional regulator protein. AIRE is expressed in the medullary epithelial cells and monocyte-dendritic cells of the thymus with lower expression in the spleen, fetal liver, and lymph nodes. At the cellular level, AIRE is located in microtubular structures of the cytoskeleton and in discrete nuclear dots resembling ND10 nuclear bodies. We studied the determinants of the targeting of AIRE into these structures. We report here that the N-terminal HSR domain confers localization to the microtubular network whereas the C-terminal region contains a second nuclear localization signal. We also demonstrate that the consensus nuclear localization signal of AIRE is functional and that the HSR domain harbors a nuclear export signal. Accordingly, the nuclear export inhibitor leptomycin B partially inhibits the nuclear export of AIRE. From a functional standpoint, we show that AIRE can activate the interferon beta minimal promoter in a transfection assay and demonstrate that the transcriptional activating function of AIRE is mediated by its two plant homeodomain (PHD) zinc fingers.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Jun
|
|
pubmed:issn |
0021-9258
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
1
|
|
pubmed:volume |
276
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
19597-602
|
|
pubmed:dateRevised |
2008-11-21
|
|
pubmed:meshHeading |
pubmed-meshheading:11274163-Animals,
pubmed-meshheading:11274163-COS Cells,
pubmed-meshheading:11274163-Cell Nucleus,
pubmed-meshheading:11274163-Cytoskeleton,
pubmed-meshheading:11274163-Epithelial Cells,
pubmed-meshheading:11274163-Fatty Acids, Unsaturated,
pubmed-meshheading:11274163-Humans,
pubmed-meshheading:11274163-Liver,
pubmed-meshheading:11274163-Lymph Nodes,
pubmed-meshheading:11274163-Microscopy, Fluorescence,
pubmed-meshheading:11274163-Microtubules,
pubmed-meshheading:11274163-Mutation,
pubmed-meshheading:11274163-Nuclear Localization Signals,
pubmed-meshheading:11274163-Plasmids,
pubmed-meshheading:11274163-Promoter Regions, Genetic,
pubmed-meshheading:11274163-Protein Binding,
pubmed-meshheading:11274163-Protein Structure, Tertiary,
pubmed-meshheading:11274163-Protein Transport,
pubmed-meshheading:11274163-Spleen,
pubmed-meshheading:11274163-Thymus Gland,
pubmed-meshheading:11274163-Transcription, Genetic,
pubmed-meshheading:11274163-Transcription Factors,
pubmed-meshheading:11274163-Transcriptional Activation,
pubmed-meshheading:11274163-Transfection,
pubmed-meshheading:11274163-U937 Cells
|
|
pubmed:year |
2001
|
|
pubmed:articleTitle |
Subcellular localization of the autoimmune regulator protein. characterization of nuclear targeting and transcriptional activation domain.
|
|
pubmed:affiliation |
Institute of Medical Technology, FIN-33014 University of Tampere and Department of Pathology, Tampere University Hospital, Tampere, Finland.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|
