QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online March 4, 2009

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?

How Wnts keep Ras in check

Aberrant activation of the GTPase Ras – which regulates cell proliferation – is a major cause of human cancer, so diverse signalling mechanisms exist to regulate its activity. For instance, Kang-Yell Choi and colleagues previously showed that Wnt/β-catenin signalling regulates the degradation of the H-Ras isoform; now, they report on the underlying mechanism of this process (p. 842). The authors show that, in HEK293 cells, endogenous and overexpressed H-Ras are polyubiquitylated and degraded by the proteasome. Moreover, these processes are mediated by β-transducin-repeat-containing protein (β-TrCP) – a key subunit of the SCF E3 ubiquitin-ligase complex. Next, the authors show that Axin and APC, which are negative regulators of the Wnt/β-catenin pathway, destabilise H-Ras by enhancing its interaction with β-TrCP; by contrast, binding of β-TrCP to H-Ras, and polyubiquitylation of H-Ras, are both reduced in cells treated with Wnt3a. In colorectal cancer cells, H-Ras-dependent proliferation is reduced by β-TrCP. Importantly, mice treated intravenously with Wnt3a have higher levels of Ras and β-catenin than untreated controls. Together, these data indicate a novel mechanism for the regulation of H-Ras stability. Ras destabilisation by Wnt/β-catenin signalling might, the authors propose, act as a safeguard against tumourigenesis.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

Related articles in JCS:

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

Sung-Eun Kim, Ju-Yong Yoon, Woo-Jeong Jeong, Soung-Hoo Jeon, Yoon Park, Jong-Bok Yoon, Y. N. Park, Hoguen Kim, and Kang-Yell Choi
JCS 2009 122: 842-848. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?