Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-2-4
pubmed:databankReference
pubmed:abstractText
Embryonic stem (ES) cells are pluripotent cells derived from the inner cell mass of blastocysts. Self-renewal of mouse ES cells depends on activation of Stat3 by leukaemia inhibitory factor (LIF) in collaboration with bone morphogenetic protein signalling. The transcription factor Nanog is essential in maintaining pluripotency but the mechanisms involved are poorly understood. Here we examine the functional interactions of Nanog with the Stat3 and NFkappaB pathways. Nanog and Stat3 were found to bind to and synergistically activate Stat3-dependent promoters. We also found that Nanog binds to NFkappaB proteins; however, Nanog binding inhibited transcriptional activity of NFkappaB proteins. Endogenous NFkappaB activity and target-gene expression increased during differentiation of ES cells. Overexpression of NFkappaB proteins promoted differentiation, whereas inhibition of NFkappaB signalling, either by genetic ablation of the Ikbkg gene or overexpression of the IkappaBalpha super-repressor, increased expression of pluripotency markers. We conclude that Nanog represses the pro-differentiation activities of NFkappaB and cooperates with Stat3 to maintain pluripotency.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1476-4679
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
194-201
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Nanog maintains pluripotency of mouse embryonic stem cells by inhibiting NFkappaB and cooperating with Stat3.
pubmed:affiliation
Wellcome Trust Centre for Stem Cell Research, Tennis Court Road, Cambridge CB2 1QR, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't