This Article Full Text (PDF) All Versions of this Article: 1087057105275983v1 10/6/590    most recent References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Larson, C. J. Articles by Negro-Vilar, A. Search for Related Content PubMed PubMed Citation Articles by Larson, C. J. Articles by Negro-Vilar, A. Social Bookmarking                   What's this?

Peptide Binding Identifies an ER Conformation That Generates Selective Activity in Multiple In Vitro Assays

Departments of Molecular & Cell Biology and New Leads Discovery Ligand Pharmaceuticals, San Diego, CA

Deborah L. Osburn

Departments of Molecular & Cell Biology and New Leads Discovery Ligand Pharmaceuticals, San Diego, CA

Katherine Schmitz

Departments of Molecular & Cell Biology and New Leads Discovery Ligand Pharmaceuticals, San Diego, CA

Leslie Giampa

Departments of Molecular & Cell Biology and New Leads Discovery Ligand Pharmaceuticals, San Diego, CA

Shau-Ming Mong

Departments of Molecular & Cell Biology and New Leads Discovery Ligand Pharmaceuticals, San Diego, CA

Keith Marschke

Departments of Molecular & Cell Biology and New Leads Discovery Ligand Pharmaceuticals, San Diego, CA

H. Martin Seidel

Departments of Molecular & Cell Biology and New Leads Discovery Ligand Pharmaceuticals, San Diego, CA

Jonathan Rosen

Departments of Molecular & Cell Biology and New Leads Discovery Ligand Pharmaceuticals, San Diego, CA

Andrés Negro-Vilar

Departments of Molecular & Cell Biology and New Leads Discovery Ligand Pharmaceuticals, San Diego, CA

Drugs such as tamoxifen, which act at the estrogen receptor (ER), have very different in vitro and in vivo effects from those of the native hormone. Previous research has established that different ligands induce distinct conformational changes in the ER, thus affecting the interactions of the receptor with cell-specific coactivating or corepressing proteins (cofactors) and estrogen response elements (EREs), thus potentially driving differing biological effects. Affinity-selected peptides have been used to probe the conformational changes that occur within the ER upon binding various ligands. In this study, the authors characterize the ability of several peptides to be recruited to liganded ER under cellular conditions. Approximating ER conformation via recruitment of this peptide to the ER is concluded to be a better predictor of the agonist nature of an ER ligand under these different cellular contexts than is a canonical cotransfection transactivation assay.

Key Words: agonism • Gal4 DNA-binding domain • ligand-binding domain • nuclear receptor • selective estrogen receptor modulator

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. M. Hall and D. P. McDonnell Coregulators in Nuclear Estrogen Receptor Action: From Concept to Therapeutic Targeting Mol. Interv., December 1, 2005; 5(6): 343 - 357. [Abstract] [Full Text] [PDF]