Maintenance has been completed and SciCrunch services have been restored. We apologize for any inconvenience it may have caused.

Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

The KLHL12-Cullin-3 ubiquitin ligase negatively regulates the Wnt-beta-catenin pathway by targeting Dishevelled for degradation.

Dishevelled is a conserved protein that interprets signals received by Frizzled receptors. Using a tandem-affinity purification strategy and mass spectrometry we have identified proteins associated with Dishevelled, including a Cullin-3 ubiquitin ligase complex containing the Broad Complex, Tramtrack and Bric à Brac (BTB) protein Kelch-like 12 (KLHL12). This E3 ubiquitin ligase complex is recruited to Dishevelled in a Wnt-dependent manner that promotes its poly-ubiquitination and degradation. Functional analyses demonstrate that regulation of Dishevelled by this ubiquitin ligase antagonizes the Wnt-beta-catenin pathway in cultured cells, as well as in Xenopus and zebrafish embryos. Considered with evidence that the distinct Cullin-1 based SCF(beta-TrCP)complex regulates beta-catenin stability, our data on the stability of Dishevelled demonstrates that two distinct ubiquitin ligase complexes regulate the Wnt-beta-catenin pathway.

Pubmed ID: 16547521

Authors

  • Angers S
  • Thorpe CJ
  • Biechele TL
  • Goldenberg SJ
  • Zheng N
  • MacCoss MJ
  • Moon RT

Journal

Nature cell biology

Publication Data

April 11, 2006

Associated Grants

  • Agency: NCRR NIH HHS, Id: P41 RR011823

Mesh Terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Blotting, Western
  • Carrier Proteins
  • Cell Cycle Proteins
  • Cell Line
  • Chromatography, Affinity
  • Cullin Proteins
  • Embryo, Nonmammalian
  • Fluorescent Antibody Technique, Indirect
  • Humans
  • Kidney
  • Microscopy, Fluorescence
  • Phosphoproteins
  • Signal Transduction
  • Ubiquitin
  • Ubiquitin-Protein Ligases
  • Wnt Proteins
  • Xenopus Proteins
  • Xenopus laevis
  • Zebrafish
  • Zebrafish Proteins
  • beta Catenin