Linked Life Data

10224118

Source:http://linkedlifedata.com/resource/pubmed/id/10224118

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
19
pubmed:dateCreated
1999-6-3
pubmed:abstractText
Mutant K246A in the predicted helix 3 of the ligand-binding domain, as well as mutants L417S and E420Q in helix 12, which contains the core ligand-dependent transcriptional activation domain (AF-2), were generated to examine AF-2 activity of the vitamin D receptor (VDR). These mutations abolished vitamin D-dependent transactivation. In addition, VDR mediates a ligand-dependent repression of the response of the retinoic acid receptor beta2 promoter to retinoic acid, and the helix 3 and helix 12 mutants were unable to mediate transrepression. Furthermore, the VDR mutants, but not the native receptor, enhanced phorbol ester induction of the activator protein-1-containing collagenase promoter. The helix 3 and helix 12 mutations strikingly reduced the ability of VDR to interact with the coactivators steroid receptor coactivator-1, ACTR, and the CREB-binding protein. As a consequence, overexpression of steroid receptor coactivator-1 increased vitamin D-dependent transactivation by VDR but not by the K246A mutant. These results indicate that the lysine 246 participates, together with residues in helix 12, in the recruitment of coactivators and that AF-2 activity is involved both in ligand-dependent transactivation and in transrepression by VDR.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
7
pubmed:volume
274
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
13503-10
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:10224118-Amino Acid Sequence, pubmed-meshheading:10224118-Base Sequence, pubmed-meshheading:10224118-Collagenases, pubmed-meshheading:10224118-DNA Primers, pubmed-meshheading:10224118-Histone Acetyltransferases, pubmed-meshheading:10224118-Humans, pubmed-meshheading:10224118-Ligands, pubmed-meshheading:10224118-Lysine, pubmed-meshheading:10224118-Molecular Sequence Data, pubmed-meshheading:10224118-Mutagenesis, Site-Directed, pubmed-meshheading:10224118-Nuclear Receptor Coactivator 1, pubmed-meshheading:10224118-Promoter Regions, Genetic, pubmed-meshheading:10224118-Protein Binding, pubmed-meshheading:10224118-Receptors, Calcitriol, pubmed-meshheading:10224118-Sequence Homology, Amino Acid, pubmed-meshheading:10224118-Transcription, Genetic, pubmed-meshheading:10224118-Transcription Factors
pubmed:year
1999
pubmed:articleTitle
Lysine 246 of the vitamin D receptor is crucial for ligand-dependent interaction with coactivators and transcriptional activity.
pubmed:affiliation
Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, 28029 Madrid, Spain.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't