Linked Life Data

21804532

Source:http://linkedlifedata.com/resource/pubmed/id/21804532

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
18
pubmed:dateCreated
2011-9-14
pubmed:abstractText
C/EBP? is an auto-repressed protein that becomes post-translationally activated by Ras-MEK-ERK signalling. C/EBP? is required for oncogene-induced senescence (OIS) of primary fibroblasts, but also displays pro-oncogenic functions in many tumour cells. Here, we show that C/EBP? activation by H-Ras(V12) is suppressed in immortalized/transformed cells, but not in primary cells, by its 3' untranslated region (3'UTR). 3'UTR sequences inhibited Ras-induced cytostatic activity of C/EBP?, DNA binding, transactivation, phosphorylation, and homodimerization, without significantly affecting protein expression. The 3'UTR suppressed induction of senescence-associated C/EBP? target genes, while promoting expression of genes linked to cancers and TGF? signalling. An AU-rich element (ARE) and its cognate RNA-binding protein, HuR, were required for 3'UTR inhibition. These components also excluded the Cebpb mRNA from a perinuclear cytoplasmic region that contains activated ERK1/2, indicating that the site of C/EBP? translation controls de-repression by Ras signalling. Notably, 3'UTR inhibition and Cebpb mRNA compartmentalization were absent in primary fibroblasts, allowing Ras-induced C/EBP? activation and OIS to proceed. Our findings reveal a novel mechanism whereby non-coding mRNA sequences selectively regulate C/EBP? activity and suppress its anti-oncogenic functions.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1460-2075
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3714-28
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
3'UTR elements inhibit Ras-induced C/EBP? post-translational activation and senescence in tumour cells.
pubmed:affiliation
Laboratory of Cancer Prevention, Center for Cancer Research, National Cancer Institute-Frederick, NIH, MD, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Intramural