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C/EBPbetaDeltauORF mice--a genetic model for uORF-mediated translational control in mammals

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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
Publisher:Cold Spring Harbor Laboratory Press
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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