Linked Life Data

20970343

Source:http://linkedlifedata.com/resource/pubmed/id/20970343

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
21
pubmed:dateCreated
2010-11-8
pubmed:databankReference
pubmed:abstractText
Overexpression of Dishevelled (Dvl), an essential component of the Wnt signaling pathway, is frequently associated with tumors, and thus the Dvl protein level must be tightly controlled to sustain Wnt signaling without causing tumors. Kelch-like 12 (KLHL12) targets Dvl for ubiquitination and degradation, suggesting its potential importance in avoiding aberrant Dvl overexpression. However, the regulatory mechanism of the KLHL12 activity remained elusive. We show here that nucleoredoxin (NRX) determines the Dvl protein level, which is revealed by analyses on NRX(-/-) mice showing skeletal and cardiovascular defects. Consistent with the previously reported Dvl-inhibiting function of NRX, Wnt/?-catenin signaling is hyperactivated in NRX(-/-) osteoblasts. However, the signal activity is suppressed in cardiac cells, where KLHL12 is highly expressed. Biochemical analyses reveal that Dvl is rapidly degraded by accelerated ubiquitination in NRX(-/-) mouse embryonic fibroblasts, and they fail to activate Wnt/?-catenin signaling in response to Wnt ligands. Moreover, experiments utilizing purified proteins show that NRX expels KLHL12 from Dvl and inhibits ubiquitination. These findings reveal an unexpected function of NRX, retaining a pool of inactive Dvl for robust activation of Wnt/?-catenin signaling upon Wnt stimulation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1879-0445
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
9
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1945-52
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Nucleoredoxin sustains Wnt/?-catenin signaling by retaining a pool of inactive dishevelled protein.
pubmed:affiliation
Laboratory of Intracellular Signaling, Institute for Protein Research, Osaka University, Suita, Osaka 565-0871, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't