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Beta-catenin gets jaded and von Hippel-Lindau is to blame

Jason D Berndt1, Randall T Moon, Michael B Major

  • 1Howard Hughes Medical Institute, Department of Pharmacology and Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Box 357370, Seattle, WA 98109, USA. jdberndt@u.washington.edu

Trends in Biochemical Sciences
|February 17, 2009
PubMed

Insights

The von Hippel-Lindau (VHL) tumor suppressor interacts with Wnt-beta-catenin signaling. VHL loss in clear cell renal cell carcinoma may cause tumors by preventing Jade-1 from degrading beta-catenin.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • The von Hippel-Lindau (VHL) tumor suppressor is implicated in Wnt-beta-catenin signaling.
  • The precise mechanism of VHL and Wnt pathway crosstalk is not fully understood.
  • VHL is known to stabilize Jade-1 protein levels.

Purpose of the Study:

  • To elucidate the mechanism of interaction between VHL and the Wnt-beta-catenin signaling cascade.
  • To investigate the role of Jade-1 in the VHL-mediated regulation of beta-catenin.

Main Methods:

  • Ubiquitylation assays were performed to assess Jade-1's effect on beta-catenin.
  • Protein degradation studies were conducted to confirm the impact of Jade-1 ubiquitylation.
  • VHL's role in stabilizing Jade-1 was examined in the context of clear cell renal cell carcinoma.

Main Results:

  • Jade-1 was found to ubiquitylate beta-catenin.
  • Ubiquitylation by Jade-1 leads to the degradation of beta-catenin.
  • Loss of VHL function, observed in clear cell renal cell carcinoma, correlates with de-repression of beta-catenin.

Conclusions:

  • Jade-1 acts as a key mediator in the VHL-Wnt pathway crosstalk.
  • Jade-1-mediated beta-catenin degradation is a VHL-dependent process.
  • Disruption of this pathway due to VHL loss contributes to clear cell renal cell carcinoma development.

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