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Related Experiment Videos

Fbw7/hCDC4 dimerization regulates its substrate interactions.

Markus Welcker1, Bruce E Clurman

  • 1Division of Human Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, Washington 98109, USA. mwelcker@fhcrc.org

Cell Division
|February 15, 2007
PubMed
Summary
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Fbw7 ubiquitin ligase dimerization is essential for degrading oncogenes like cyclin E. However, additional phosphorylation can bypass this dimerization requirement, revealing a new regulatory mechanism for Fbw7 function.

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Cell Biology

Background:

  • Fbw7 ubiquitin ligase targets key oncogenes (cyclin E, c-Myc, c-Jun, Notch) for degradation.
  • Fission yeast Fbw7 homologs (pop1, pop2) are known to dimerize.

Purpose of the Study:

  • To investigate if human Fbw7 dimerizes.
  • To determine the functional impact of Fbw7 dimerization on oncogene degradation.

Main Methods:

  • Investigated Fbw7 self-binding.
  • Assessed the role of dimerization in Fbw7-cyclin E interaction.
  • Analyzed the effect of phospho-degron modification on Fbw7 binding.

Main Results:

  • Fbw7 efficiently binds to itself via a domain near its F-box.

Related Experiment Videos

  • Fbw7 dimerization is crucial for stable interaction with the cyclin E T380 phospho-degron.
  • Increased phosphorylation at S384 on the cyclin E phospho-degron can overcome the need for Fbw7 dimerization.

    • Conclusions:

    • Fbw7-mediated cyclin E degradation is regulated by either Fbw7 dimerization or hyperphosphorylation of the T380 phospho-degron.
    • Substrates lacking specific phospho-degron features may rely solely on Fbw7 dimerization for turnover.
    • Identified a novel regulatory layer controlling Fbw7 substrate interaction and degradation.