ArrayExpress Uploaderarrayexpress_sid6543infected with retroviruses expressing H-RasV12infected with retroviruses expressing H-RasV13infected with retroviruses expressing H-RasV14infected with retroviruses expressing H-RasV12 and C/EBPβinfected with retroviruses expressing H-RasV12 and C/EBPβinfected with retroviruses expressing H-RasV12 and C/EBPβinfected with retroviruses expressing H-RasV12 and C/EBPβ-UTRinfected with retroviruses expressing H-RasV12 and C/EBPβ-UTRinfected with retroviruses expressing H-RasV12 and C/EBPβ-UTR06C/EBPb is an auto-repressed protein that becomes posttranslationally activated by Ras-MEK-ERK signalling. C/EBPb is required for...E-GEOD-30834/profile/8773/arrayexpressuploader19proteinDec.12, 2014Falseinfluence-of-cebp-3utr-on-rasv12-induced-gene-exprE-GEOD-30834_A-AFFY-45Influence of C/EBPβ 3'UTR on RasV12 induced gene expressionNov.11, 2014C/EBPb is an auto-repressed protein that becomes posttranslationally activated by Ras-MEK-ERK signalling. C/EBPb 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/EBPb activation by H-RasV12 is suppressed in immortalized/transformed cells, but not in primary cells, by its 30 untranslated region (30UTR). 30UTR sequences inhibited Ras-induced cytostatic activity of C/EBPb, DNA binding, transactivation, phosphorylation, and homodimerization, without significantly affecting protein expression. The 30UTR suppressed induction of senescence-associated C/EBPb target genes, while promoting expression of genes linked to cancers and TGFb signalling. An AU-rich element (ARE) and its cognate RNA-binding protein, HuR, were required for 30UTR inhibition. These components also excluded the Cebpb mRNA from a perinuclear cytoplasmic region that contains activated ERK1/2, indicating that the site of C/EBPb translation controls de-repression by Ras signalling. Notably, 30UTR inhibition and Cebpb mRNA compartmentalization were absent in primary fibroblasts, allowing Ras-induced C/EBPb activation and OIS to proceed. Our findings reveal a novel mechanism whereby non-coding mRNA sequences selectively regulate C/EBPb activity and suppress its anti-oncogenic functions. NIH-3T3 cells were retrovirally infected and selected with appropriate antiobiotics. Equal number of cells were plated and collected 48-72 hours later.http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-30834mousehttp://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-30834/samples/