Linked Life Data

7491109

Source:http://linkedlifedata.com/resource/pubmed/id/7491109

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
1996-1-4
pubmed:abstractText
Residues located between amino acids 244 and 263 in the human vitamin D receptor (hVDR) show extensive homology with other members of the steroid/thyroid/retinoid hormone receptor superfamily. The corresponding region of the glucocorticoid receptor has been shown to interact with the 90-kilodalton heat shock protein (hsp90), yet hVDR does not appear to bind to hsp90. Herein we report a study of hVDR in which the functional role of five conserved residues was tested by replacing Phe-244, Lys-246, Leu-254, Gln-259, and Leu-262 with glycines by site-directed mutagenesis. Initial screening of these mutants indicated that all were significantly impaired in their ability to activate transcription from a vitamin D-responsive reporter construct when expressed in transfected VDR-deficient COS-7 cells. Further characterization revealed two classes of mutants: the predominant class binds the 1,25-dihydroxyvitamin D3 ligand normally but is defective in its ability to form a heterodimeric complex with the retinoid X receptor (RXR) on a vitamin D responsive element (VDRE). A second unique class, represented by a single mutant at Lys-246, is normal both with respect to ligand binding and complex formation but still very impaired in transactivation ability. The distinction between these two classes was confirmed by the demonstration that a member of the first class, with a mutation at Gln-259, could be restored to near wild type transactivation ability by supplying excess RXR, while the Lys-246 mutant could not be so rescued. We therefore conclude that the primary function of this conserved domain in hVDR is the mediation of heterodimerization with RXR, leading to VDRE binding and transactivation. The possibility also exists that the Lys-246 mutant may be impaired in a step of transactivation that is distal to complex formation with RXR on the VDRE, perhaps in interactions with the transcriptional machinery itself.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0888-8809
pubmed:author
pubmed:issnType
Print
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1166-79
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:7491109-Amino Acid Sequence, pubmed-meshheading:7491109-Animals, pubmed-meshheading:7491109-Base Sequence, pubmed-meshheading:7491109-Binding Sites, pubmed-meshheading:7491109-Calcitriol, pubmed-meshheading:7491109-Cell Line, Transformed, pubmed-meshheading:7491109-Cercopithecus aethiops, pubmed-meshheading:7491109-Conserved Sequence, pubmed-meshheading:7491109-Hormones, pubmed-meshheading:7491109-Humans, pubmed-meshheading:7491109-Kidney, pubmed-meshheading:7491109-Macromolecular Substances, pubmed-meshheading:7491109-Molecular Sequence Data, pubmed-meshheading:7491109-Mutagenesis, Site-Directed, pubmed-meshheading:7491109-Point Mutation, pubmed-meshheading:7491109-Receptors, Calcitriol, pubmed-meshheading:7491109-Receptors, Retinoic Acid, pubmed-meshheading:7491109-Retinoid X Receptors, pubmed-meshheading:7491109-Simian virus 40, pubmed-meshheading:7491109-Structure-Activity Relationship, pubmed-meshheading:7491109-Transcription, Genetic, pubmed-meshheading:7491109-Transcription Factors, pubmed-meshheading:7491109-Transfection
pubmed:year
1995
pubmed:articleTitle
A highly conserved region in the hormone-binding domain of the human vitamin D receptor contains residues vital for heterodimerization with retinoid X receptor and for transcriptional activation.
pubmed:affiliation
Department of Biochemistry, University of Arizona College of Medicine, Tucson 85724, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.