Linked Life Data

12471056

Source:http://linkedlifedata.com/resource/pubmed/id/12471056

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
26
pubmed:dateCreated
2002-12-9
pubmed:abstractText
Mutations in the human autoimmune regulator (AIRE ) gene cause a multi-systemic autoimmune syndrome that is known as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). To date more than 39 different disease mutations have been identified. They span the entire region of the AIRE gene that encodes a polypeptide with multiple functional domains: an N-terminal homogeneously staining region (HSR), a bipartied nuclear localization signal (NLS), a SAND domain, two PHD fingers and four nuclear receptor targeting motifs. The APECED mutations include insertions, deletions, substitutions and introduction of premature termination codons, while most mutations disrupt one of the functional domains. We have constructed a series of deletion mutants systematically removing one or more functional domain(s) and investigated the stability and sub-cellular compartmentalization of the corresponding polypeptides. Here we show that the first 188 amino acids, containing the HSR domain and the NLS proved necessary for both cytoplasmic filament formation and nuclear targeting. Deletion of the SAND domain and even point mutations in the SAND domain, resulted in the aggregation of the polypeptides in the cytoplasm and interfered with the proper nuclear targeting. The PHD fingers seemed to be necessary for the formation of characteristic dot-like complexes in the nucleus, but their deletion did not interfere with nuclear entry.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0964-6906
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3299-308
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Systematic mutagenesis of the functional domains of AIRE reveals their role in intracellular targeting.
pubmed:affiliation
Department of Human Genetics, UCLA School of Medicine, Gonda Center, University of California Los Angeles, Los Angeles, California, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't