Linked Life Data

21303975

Source:http://linkedlifedata.com/resource/pubmed/id/21303975

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2011-2-17
pubmed:abstractText
Raf kinase inhibitory protein (RKIP) is a physiologic inhibitor of c-RAF kinase and nuclear factor ?B signaling that represses tumor invasion and metastasis. Glycogen synthase kinase-3? (GSK3?) suppresses tumor progression by downregulating multiple oncogenic pathways including Wnt signaling and cyclin D1 activation. Here, we show that RKIP binds GSK3 proteins and maintains GSK3? protein levels and its active form. Depletion of RKIP augments oxidative stress-mediated activation of the p38 mitogen activated protein kinase, which, in turn, inactivates GSK3? by phosphorylating it at the inhibitory T390 residue. This pathway de-represses GSK3? inhibition of oncogenic substrates causing stabilization of cyclin D, which induces cell-cycle progression and ?-catenin, SNAIL, and SLUG, which promote epithelial to mesenchymal transition. RKIP levels in human colorectal cancer positively correlate with GSK3? expression. These findings reveal the RKIP/GSK3 axis as both a potential therapeutic target and a prognosis-based predictor of cancer progression.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1538-7445
pubmed:author
pubmed:copyrightInfo
©2011 AACR.
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
71
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1334-43
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Raf kinase inhibitor protein RKIP enhances signaling by glycogen synthase kinase-3?.
pubmed:affiliation
Department of Pathology, Faculty of Medicine, Health Sciences Center, Kuwait University, Safat, Kuwait, UK. fahd@al-mulla.org
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't