Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2005-2-11
pubmed:abstractText
Murine ES cells can be maintained as a pluripotent, self-renewing population by LIF/STAT3-dependent signaling. The downstream effectors of this pathway have not been previously defined. In this report, we identify a key target of the LIF self-renewal pathway by showing that STAT3 directly regulates the expression of the Myc transcription factor. Murine ES cells express elevated levels of Myc and following LIF withdrawal, Myc mRNA levels collapse and Myc protein becomes phosphorylated on threonine 58 (T58), triggering its GSK3beta dependent degradation. Maintained expression of stable Myc (T58A) renders self-renewal and maintenance of pluripotency independent of LIF. By contrast, expression of a dominant negative form of Myc antagonizes self-renewal and promotes differentiation. Transcriptional control by STAT3 and suppression of T58 phosphorylation are crucial for regulation of Myc activity in ES cells and therefore in promoting self-renewal. Together, our results establish a mechanism for how LIF and STAT3 regulate ES cell self-renewal and pluripotency.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0950-1991
pubmed:author
pubmed:issnType
Print
pubmed:volume
132
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
885-96
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed-meshheading:15673569-Animals, pubmed-meshheading:15673569-Blotting, Northern, pubmed-meshheading:15673569-Cell Differentiation, pubmed-meshheading:15673569-Chromatin Immunoprecipitation, pubmed-meshheading:15673569-DNA-Binding Proteins, pubmed-meshheading:15673569-Down-Regulation, pubmed-meshheading:15673569-Embryo, Mammalian, pubmed-meshheading:15673569-Flow Cytometry, pubmed-meshheading:15673569-Glycogen Synthase Kinase 3, pubmed-meshheading:15673569-Immunoblotting, pubmed-meshheading:15673569-Mice, pubmed-meshheading:15673569-Mice, Inbred C57BL, pubmed-meshheading:15673569-Mice, Transgenic, pubmed-meshheading:15673569-Models, Biological, pubmed-meshheading:15673569-Phosphorylation, pubmed-meshheading:15673569-Plasmids, pubmed-meshheading:15673569-Proto-Oncogene Proteins c-myc, pubmed-meshheading:15673569-RNA, Messenger, pubmed-meshheading:15673569-STAT3 Transcription Factor, pubmed-meshheading:15673569-Stem Cells, pubmed-meshheading:15673569-Time Factors, pubmed-meshheading:15673569-Trans-Activators, pubmed-meshheading:15673569-Transcription, Genetic, pubmed-meshheading:15673569-Transfection
pubmed:year
2005
pubmed:articleTitle
LIF/STAT3 controls ES cell self-renewal and pluripotency by a Myc-dependent mechanism.
pubmed:affiliation
University of Georgia, Rhodes Center, 425 River Road, Athens, GA 30602-2771, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't