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, Young Nyun Park, Hoguen Kim, Kang-Yell Choi

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)842-848
Number of pages7
JournalJournal of cell science
Volume122
Issue number6
DOIs
Publication statusPublished - 2009 Mar 15

Fingerprint

Catenins
ras Proteins
Wnt Signaling Pathway
Adenomatous Polyposis Coli
MAP Kinase Signaling System
Ubiquitination
Guanosine Triphosphate
Intestines
Tail
Veins
Injections
Proteins

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Kim, Sung Eun ; Yoon, Ju Yong ; Jeong, Woo Jeong ; Jeon, Soung Hoo ; Park, Yoon ; Yoon, Jong-Bok ; Park, Young Nyun ; Kim, Hoguen ; Choi, Kang-Yell. / H-Ras is degraded by Wnt/β-catenin signaling via β-TrCP-mediated polyubiquitylation. In: Journal of cell science. 2009 ; Vol. 122, No. 6. pp. 842-848.
@article{a14c987ddcb843aeb2dc99b390de5f6c,
title = "H-Ras is degraded by Wnt/β-catenin signaling via β-TrCP-mediated polyubiquitylation",
abstract = "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.",
author = "Kim, {Sung Eun} and Yoon, {Ju Yong} and Jeong, {Woo Jeong} and Jeon, {Soung Hoo} and Yoon Park and Jong-Bok Yoon and Park, {Young Nyun} and Hoguen Kim and Kang-Yell Choi",
year = "2009",
month = "3",
day = "15",
doi = "10.1242/jcs.040493",
language = "English",
volume = "122",
pages = "842--848",
journal = "Journal of Cell Science",
issn = "0021-9533",
publisher = "Company of Biologists Ltd",
number = "6",

}

H-Ras is degraded by Wnt/β-catenin signaling via β-TrCP-mediated polyubiquitylation. / Kim, Sung Eun; Yoon, Ju Yong; Jeong, Woo Jeong; Jeon, Soung Hoo; Park, Yoon; Yoon, Jong-Bok; Park, Young Nyun; Kim, Hoguen; Choi, Kang-Yell.

In: Journal of cell science, Vol. 122, No. 6, 15.03.2009, p. 842-848.

Research output: Contribution to journalArticle

TY - JOUR

T1 - H-Ras is degraded by Wnt/β-catenin signaling via β-TrCP-mediated polyubiquitylation

AU - Kim, Sung Eun

AU - Yoon, Ju Yong

AU - Jeong, Woo Jeong

AU - Jeon, Soung Hoo

AU - Park, Yoon

AU - Yoon, Jong-Bok

AU - Park, Young Nyun

AU - Kim, Hoguen

AU - Choi, Kang-Yell

PY - 2009/3/15

Y1 - 2009/3/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=66949151103&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=66949151103&partnerID=8YFLogxK

U2 - 10.1242/jcs.040493

DO - 10.1242/jcs.040493

M3 - Article

VL - 122

SP - 842

EP - 848

JO - Journal of Cell Science

JF - Journal of Cell Science

SN - 0021-9533

IS - 6

ER -