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| Item Type: | Article |
|---|---|
| Title: | C/EBPbetaDeltauORF mice--a genetic model for uORF-mediated translational control in mammals |
| Creators Name: | Wethmar, K., Bégay, V., Smink, J.J., Zaragoza, K., Wiesenthal, V., Doerken, B., Calkhoven, C.F. and Leutz, A. |
| Abstract: | Upstream ORFs (uORFs) are translational control elements found predominantly in transcripts of key regulatory genes. No mammalian genetic model exists to experimentally validate the physiological relevance of uORF-regulated translation initiation. We report that mice deficient for the CCAAT/enhancer-binding protein beta (C/EBPbeta) uORF initiation codon fail to initiate translation of the autoantagonistic LIP (liver inhibitory protein) C/EBPbeta isoform. C/EBPbeta(DeltauORF) mice show hyperactivation of acute-phase response genes, persistent repression of E2F-regulated genes, delayed and blunted S-phase entry of hepatocytes after partial hepatectomy, and impaired osteoclast differentiation. These data and the widespread prevalence of uORFs in mammalian transcriptomes suggest a comprehensive role of uORF-regulated translation in (patho)physiology. |
| Keywords: | Upstream ORF, Translational Control, C/EBPbeta, Liver Regeneration, Cell Cycle, Animals, Mice |
| Source: | Genes & Development |
| ISSN: | 0890-9369 |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Volume: | 24 |
| Number: | 1 |
| Page Range: | 15-20 |
| Date: | 1 January 2010 |
| Official Publication: | https://doi.org/10.1101/gad.557910 |
| PubMed: | View item in PubMed |
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