Linked Life Data

10385402

Source:http://linkedlifedata.com/resource/pubmed/id/10385402

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
1999-7-15
pubmed:abstractText
Despite the wide spectrum of androgen receptor (AR) mutants described in androgen insensitivity syndromes (AIS), their influence on transactivating and, in particular, transrepressing functions of AR are poorly defined. Rat AR mutants with substitutions in the DNA-binding domain, corresponding to several mutations in AIS patients, were examined for these activities. AR variants (G551V and C562G) with mutations in the first zinc finger (ZF) exhibited reduced DNA binding activity and attenuated transactivation. An R590Q substitution in the second ZF diminished transcriptional activity only from a promoter with a single androgen response element, whereas activation at multiple androgen response element sites was unaffected, despite the poor DNA-binding affinity of R590Q. Another substitution in the second ZF, A579T, yielded similar findings. In comparison to wild-type AR, G551V, and C562G variants had markedly reduced ability to repress an NF-kappaB/RelA-activated promoter but R590Q behaved like the native receptor. AP1 function was repressed not only by wild-type AR but also by the transactivating mutants A579T and R590Q as well as by the transcriptionally inactive mutants G551V and C562G. Furthermore, a Lys-to-Ala substitution in codon 563 of the first ZF switched AR into a ligand-dependent activator at AP1 sites but maintained the ability to repress NF-kappaB/RelA function. Taken together, DNA-binding domain mutations in AIS patients influence transcriptional activating and repressing functions of AR in a selective fashion, which probably contributes to the complexity in the presentation of the AIS phenotype.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
140
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3097-105
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Transcription activating and repressing functions of the androgen receptor are differentially influenced by mutations in the deoxyribonucleic acid-binding domain.
pubmed:affiliation
Department of Physiology, Institute of Biomedicine, University of Helsinki, Finland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't