Analysis of ligand-dependent recruitment of coactivator peptides to estrogen receptor using fluorescence polarization

Molecular Endocrinology
Mary Szatkowski OzersThomas J Burke

Abstract

Ligand-dependent recruitment of coactivators to estrogen receptor (ER) plays an important role in transcriptional activation of target genes. Agonist-bound ER has been shown to adopt a favorable conformation for interaction with the LXXLL motifs of the coactivator proteins. To further examine the affinity and ligand dependence of the ER-coactivator interaction, several fluorescently tagged short peptides bearing an LXXLL motif (LXXLL peptide) from either natural coactivator sequences or random phage display sequences were used with purified ERalpha or ERbeta in an in vitro high-throughput fluorescence polarization assay. In the presence of saturating amounts of ligand, several LXXLL peptides bound to ERalpha and ERbeta with affinity ranging from 20-500 nm. The random phage display LXXLL peptides exhibited a higher affinity for ER than the natural single-LXXLL coactivator sequences tested. These studies indicated that ER agonists, such as 17beta-estradiol or estrone, promoted the interaction of ER with the coactivator peptides, whereas antagonists such as 4-hydroxytamoxifen or ICI-182,780 did not. Different LXXLL peptides demonstrated different affinities for ER depending on which ligand was bound to the receptor, suggesting tha...Continue Reading

References

May 14, 1996·Proceedings of the National Academy of Sciences of the United States of America·H HongM R Stallcup
Jun 1, 1996·Molecular Endocrinology·J R LundbladR H Goodman
Aug 5, 1997·Proceedings of the National Academy of Sciences of the United States of America·H LiJ D Chen
Mar 31, 1999·Proceedings of the National Academy of Sciences of the United States of America·L A PaigeD M Fowlkes
Jul 31, 1999·Science·J D NorrisD P McDonnell
Mar 9, 2000·Molecular Endocrinology·D RobyrW Wahli
Jun 6, 2000·Journal of Biomolecular Screening·J H ZhangK R Oldenburg
Mar 16, 2001·Structure·A C PikeM Carlquist
Jan 30, 2003·Molecular Endocrinology·Jianwei LiuClay W Scott
Apr 8, 2003·Combinatorial Chemistry & High Throughput Screening·T J BurkeK M Ervin
Jun 14, 2003·Molecular Endocrinology·Jianming Xu, Qingtian Li
Jan 23, 2004·Journal of Medicinal Chemistry·Alice L RodriguezJohn A Katzenellenbogen

❮ Previous
Next ❯

Citations

Sep 13, 2011·Toxicological Sciences : an Official Journal of the Society of Toxicology·Michael S DenisonBin Zhao
Feb 9, 2012·International Journal of Molecular Sciences·Paweł SzymańskiElżbieta Mikiciuk-Olasik
Sep 19, 2012·Biotechnology Letters·Tuomas HuovinenTeijo Pellinen
May 25, 2011·Molecular and Cellular Endocrinology·Mikhail N ZakharovRavi Jasuja
Dec 8, 2007·Toxicology and Applied Pharmacology·Keith A Houck, Robert J Kavlock
Oct 4, 2005·American Journal of Physiology. Heart and Circulatory Physiology·Rajesh G MishraR Kent Hermsmeyer
Nov 1, 2008·Journal of Medicinal Chemistry·Susanna RepoMark S Johnson
Nov 17, 2009·Journal of Cell Science·Jéröme EeckhouteGilles Salbert
Jun 24, 2008·ACS Chemical Biology·Ross V Weatherman

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.