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
  1. Home
  3. Research Domains

SRC-3 coactivator functional lifetime is regulated by a phospho-dependent ubiquitin time clock.

Ray-Chang Wu1, Qin Feng, David M Lonard

  • 1Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.

Cell
|June 19, 2007

Related Experiment Videos

View abstract on PubMed

Summary
This summary is machine-generated.

Related Concept Videos

  • Biomedical And Clinical Sciences
  • Oncology And Carcinogenesis
  • Predictive And Prognostic Markers
  • Src-3 Coactivator Functional Lifetime Is Regulated By A Phospho-dependent Ubiquitin Time Clock.

    • Regulated ubiquitination of SRC-3 (Steroid Receptor Coactivator-3) controls its activation and degradation. This phosphorylation-dependent process acts as a "transcriptional time clock," balancing coactivator function and preventing oncogenesis.

    Area of Science:

    • Molecular Biology
    • Biochemistry
    • Cancer Research

    Background:

    • SRC-3 (Steroid Receptor Coactivator-3)/AIB1 is a crucial growth coactivator implicated in oncogenesis when overactivated.
    • Tight regulation of SRC-3 activity is essential for normal cellular function and preventing uncontrolled growth.

    Purpose of the Study:

    • To elucidate the regulatory mechanisms governing SRC-3 coactivator activation and transcriptional specificity.
    • To investigate the role of phosphorylation-dependent ubiquitination in controlling SRC-3 function and stability.

    Main Methods:

    • Identification of a critical "actron/degron" element within SRC-3.
    • Characterization of GSK3 as the responsible kinase and SCF(Fbw7alpha) as the E3 ubiquitin ligase.
    • Analysis of SRC-3 ubiquitination patterns (multi-/mono-ubiquitination vs. polyubiquitination) and their functional consequences.

    Main Results:

    • Discovered a phosphorylation-dependent ubiquitination pathway regulating SRC-3.
    • Identified GSK3 and SCF(Fbw7alpha) in this regulatory cascade.
    • Demonstrated that SCF(Fbw7alpha) mediates both non-proteolytic activation and proteasomal degradation of SRC-3.
    • Observed a biphasic ubiquitination process transitioning from activation to degradation, acting as a "transcriptional time clock."

    Conclusions:

    • Coordinated phosphorylation and ubiquitination tightly regulate SRC-3 activity and lifespan.
    • SRC-3 ubiquitination is a biphasic event controlling coactivator activation and degradation.
    • This regulatory mechanism ensures precise control over transcriptional coactivation and prevents oncogenic overactivation.

    Related Experiment Videos