Linked Life Data

8738832

Source:http://linkedlifedata.com/resource/pubmed/id/8738832

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1997-1-7
pubmed:abstractText
Conformational differences between type I antiestrogen-liganded estrogen receptor and estradiol (E2)-liganded estrogen receptor (ER) are thought to be responsible for differentiating agonist versus antagonist ER activity at individual genes. To examine the impact of ER ligand on estrogen-response element (ERE) binding kinetics and receptor conformation, we quantitated the effect of site-directed, ER-specific antibodies raised against synthetic peptides corresponding to the DNA-binding domain of human ER on ER-ERE binding in vitro. Although 4-hydroxytamoxifen-liganded-ER (4-OHT-ER) and E2-ER bind a consensus ERE with equal high affinity, the stoichiometry of 4-OHT-ER-ERE binding at saturation is approximately 50% lower than that of E2-ER binding to all ERE sequences tested. In contrast, the ERE binding stoichiometry of tamoxifen aziridine-liganded ER (TAz-ER) is identical to that of E2-ER: one receptor dimer bound per ERE. The difference in binding stoichiometry is caused by dissociation of one molecule of 4-OHT from the ER as the dimeric receptor binds DNA. Addition of low concentrations of ER-specific polyclonal antibodies AT3A or AT3B prevented 4-OHT ligand dissociation, yielding an increase in specific 4-OHT-ER-ERE binding to a level equal to that of E2-ER- or TAz-ER-ERE binding. However, higher amounts of AT3A or AT3B inhibited specific ERE binding of both 4-OHT- and E2-ER. We conclude that differences in ER conformation when liganded with 4-OHT versus E2 are revealed by these antibodies and that such differences in receptor conformation may influence subsequent interaction of the receptor with other proteins necessary for transactivation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0039-128X
pubmed:author
pubmed:issnType
Print
pubmed:volume
61
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
278-89
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Site-directed estrogen receptor antibodies stabilize 4-hydroxytamoxifen ligand, but not estradiol, and indicate ligand-specific differences in the recognition of estrogen response element DNA in vitro.
pubmed:affiliation
Department of Biochemistry, University of Rochester School of Medicine and Dentistry, New York 14642, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't