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

E6AP and calmodulin reciprocally regulate estrogen receptor stability.

Lu Li1, Zhigang Li, Peter M Howley

  • 1Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.

The Journal of Biological Chemistry
|November 30, 2005
PubMed
Summary
This summary is machine-generated.

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

Reproducibility of the diagnosis of diabetes by the 1-hour oral glucose tolerance test is substantial.

Diabetes research and clinical practice·2026
Same author

In Support of Venous Glucose as a Reference Matrix for Evaluating Continuous Glucose Monitoring Accuracy.

Journal of diabetes science and technology·2026
Same author

HbA1c underperforms in identifying abnormal glucose tolerance in the presence of G6PD deficiency: Insight from the Africans in America study.

PloS one·2026
Same author

KSR1 is a scaffold for the Hippo signaling pathway.

Communications biology·2025
Same author

Call for modification of the intermediate hyperglycemic classification of the 1 h-oral glucose tolerance test: insight from the Africans in America cohort Commentary.

Diabetes research and clinical practice·2025
Same author

The scaffold protein IQGAP1 regulates the epithelial Na<sup>+</sup> channel.

The Journal of biological chemistry·2025

Calmodulin stabilizes the estrogen receptor (ER) by inhibiting its degradation through the ubiquitin-proteasome pathway. This interaction involves E6-associated protein (E6AP) and offers potential therapeutic targets for breast cancer.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Endocrinology

Background:

  • Estrogen receptor (ER) degradation regulates cellular responses to estrogen.
  • Calmodulin binds ER, enhancing its stability.
  • Calmodulin antagonists reduce ER levels in breast cancer cells.

Purpose of the Study:

  • Investigate the molecular mechanism of calmodulin's regulation of ER degradation.
  • Elucidate the role of the ubiquitin-proteasome pathway and E6AP in ER degradation.
  • Examine the interplay between calmodulin and E6AP in modulating ER stability.

Main Methods:

  • Utilized ubiquitin-proteasome pathway inhibitors (MG132, lactacystin) and protease inhibitors.
  • Assessed ER ubiquitination levels after calmodulin antagonist treatment.

Related Experiment Videos

  • Employed a calmodulin-binding deficient ER mutant (ERDeltaCaM).
  • Investigated in vitro interactions between ER, E6AP, and calmodulin.

    • Main Results:

    • Calmodulin antagonists increased ER ubiquitination, indicating proteasomal degradation.
    • ERDeltaCaM showed higher ubiquitination and affinity for E6AP compared to wild-type ER.
    • Calmodulin attenuated the in vitro interaction between ER and E6AP in a Ca(2+)-dependent manner.
    • E6AP was identified as a key component in ER degradation.

    Conclusions:

    • E6AP mediates ER degradation via the ubiquitin-proteasome pathway.
    • Ca(2+)/calmodulin modulates ER degradation by influencing the ER-E6AP interaction.
    • Findings suggest novel therapeutic strategies targeting ER degradation in breast cancer.