Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Estrogen receptor ligands modulate its interaction with DNA

B J Cheskis1, S Karathanasis, C R Lyttle

  • 1Women's Health Research Institute, Wyeth-Ayerst Research, Radnor, Pennsylvania 19087, USA.

The Journal of Biological Chemistry
|April 25, 1997
PubMed
Summary

Ligand binding significantly alters estrogen receptor (ER) DNA binding kinetics. Estradiol accelerates complex formation, while ICI-182,780 stabilizes it, impacting gene transcription and biological effects.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Estrogens: from classical endocrine action to tissue selective action.

Ernst Schering Research Foundation workshop·2004
Same author

Developing a SERM: stringent preclinical selection criteria leading to an acceptable candidate (WAY-140424) for clinical evaluation.

Annals of the New York Academy of Sciences·2002
Same author

A new antiestrogen, 2-(4-hydroxy-phenyl)-3-methyl-1-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-1H-indol-5-ol hydrochloride (ERA-923), inhibits the growth of tamoxifen-sensitive and -resistant tumors and is devoid of uterotropic effects in mice and rats.

Clinical cancer research : an official journal of the American Association for Cancer Research·2001
Same author

Mouse ascites golgi (MAG) mucin expression and regulation by progesterone in the rat uterus.

Journal of the Society for Gynecologic Investigation·2001
Same author

Structure-function evaluation of ER alpha and beta interplay with SRC family coactivators. ER selective ligands.

Biochemistry·2001
Same author

Design, synthesis, and preclinical characterization of novel, highly selective indole estrogens.

Journal of medicinal chemistry·2001

Area of Science:

  • Molecular Biology
  • Endocrinology
  • Genetics

Background:

  • Estrogen receptor (ER) is a ligand-inducible transcription factor.
  • ER functions like DNA binding are modulated by ligand interactions.
  • The effect of various ER ligands on DNA binding remains controversial.

Purpose of the Study:

  • To investigate the kinetics of human ER (hER) binding to its DNA element (ERE).
  • To determine how different ligands influence hER-DNA interaction dynamics.
  • To explore the correlation between ligand-induced binding kinetics and biological effects.

Main Methods:

  • Real-time interaction analysis was employed.
  • Kinetics of hER binding to ERE were measured.
  • Experiments were conducted in the absence and presence of various ER ligands, including 17beta-estradiol, 17alpha-ethynyl estradiol, tamoxifen analogs, raloxifene, and ICI-182,780.

Related Experiment Videos

Main Results:

  • Ligand binding dramatically influences the kinetics of hER-DNA interaction.
  • 17beta-estradiol binding promotes rapid formation of an unstable ER-ERE complex.
  • ICI-182,780 binding results in slow formation of a stable ER-ERE complex.
  • Estradiol accelerated complex formation frequency >50-fold vs. unliganded ER and >1000-fold vs. ICI-182,780.

Conclusions:

  • Ligand binding significantly modulates ER's DNA binding kinetics.
  • A correlation exists between the frequency of receptor-DNA complex formation and gene transcription rates.
  • The kinetics of hER-ERE interaction induced by a ligand correlate well with its biological effect.