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First published online 24 February 2009
doi: 10.1242/jcs.040493

Journal of Cell Science 122, 842-848 (2009)
Published by The Company of Biologists 2009
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Research Article

H-Ras is degraded by Wnt/β-catenin signaling via β-TrCP-mediated polyubiquitylation

Sung-Eun Kim1, Ju-Yong Yoon1, Woo-Jeong Jeong1, Soung-Hoo Jeon1, Yoon Park2, Jong-Bok Yoon2,3, Y. N. Park4, Hoguen Kim4 and Kang-Yell Choi1,3,*

1 National Research Laboratory of Molecular Complex Control and Department of Biotechnology, BK21 project for Medical Science, Yonsei University, Seoul 120-749, Korea
2 Department of Biochemistry, BK21 project for Medical Science, Yonsei University, Seoul 120-749, Korea
3 Protein Network Research Center, BK21 project for Medical Science, Yonsei University, Seoul 120-749, Korea
4 Department of Pathology, Center for Chronic Metabolic Disease, BK21 project for Medical Science, Yonsei University, Seoul 120-749, Korea

* Author for correspondence (e-mail: kychoi{at}yonsei.ac.kr)

Accepted 21 November 2008

Ras is an important proto-protein that is regulated primarily by GDP/GTP exchange. Here, we report a novel regulatory mechanism whereby turnover of both endogenous and overexpressed H-Ras protein is controlled by β-TrCP-mediated ubiquitylation, proteasomal degradation and the Wnt/β-catenin signaling pathway. The interaction of H-Ras with the WD40 domain of β-TrCP targeted H-Ras for polyubiquitylation and degradation. This process was stimulated by Axin or adenomatous polyposis coli (Apc), and was inhibited by Wnt3a. Ras-mediated cellular transformation was also inhibited by the expression of β-TrCP and/or Axin. In vivo regulation of Ras stability by Wnt/β-catenin signaling was determined via measurements of the status of Ras in the intestines of mice stimulated with recombinant Wnt3a by intravenous tail vein injection. The regulation of Ras stability by Wnt/β-catenin signaling provides a mechanical basis for crosstalk between the Wnt/β-catenin and the Ras-ERK pathways involved in transformation.

Key words: Ras, β-TrCP, Polyubiquitylation, Tumor, Wnt


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S.-E. Kim, J.-Y. Yoon, W.-J. Jeong, S.-H. Jeon, Y. Park, J.-B. Yoon, Y. N. Park, H. Kim, and K.-Y. Choi
H-Ras is degraded by Wnt/{beta}-catenin signaling via {beta}-TrCP-mediated polyubiquitylation
Development, April 1, 2009; 136(7): e1 - e1.
[Full Text]


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