Title | Peptide antagonists of the human estrogen receptor. |
Publication Type | Journal Article |
Year of Publication | 1999 |
Authors | Norris JD, Paige LA, Christensen DJ, Chang CY, Huacani MR, Fan D, Hamilton PT, Fowlkes DM, McDonnell DP |
Journal | Science |
Volume | 285 |
Issue | 5428 |
Pagination | 744-6 |
Date Published | 1999 Jul 30 |
ISSN | 0036-8075 |
Keywords | Amino Acid Sequence, Binding Sites, Estradiol, Estrogen Antagonists, Estrogen Receptor alpha, Humans, Ligands, Mifepristone, Molecular Sequence Data, Peptide Library, Peptides, Receptors, Cytoplasmic and Nuclear, Receptors, Estrogen, Recombinant Fusion Proteins, Tamoxifen, Transcription Factor AP-1, Transcription, Genetic |
Abstract | Estrogen receptor alpha transcriptional activity is regulated by distinct conformational states that are the result of ligand binding. Phage display was used to identify peptides that interact specifically with either estradiol- or tamoxifen-activated estrogen receptor alpha. When these peptides were coexpressed with estrogen receptor alpha in cells, they functioned as ligand-specific antagonists, indicating that estradiol-agonist and tamoxifen-partial agonist activities do not occur by the same mechanism. The ability to regulate estrogen receptor alpha transcriptional activity by targeting sites outside of the ligand-binding pocket has implications for the development of estrogen receptor alpha antagonists for the treatment of tamoxifen-refractory breast cancers. |
Alternate Journal | Science |
PubMed ID | 10426998 |
Grant List | DK48807 / DK / NIDDK NIH HHS / United States |
Submitted by kej2006 on June 6, 2018 - 4:10pm