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

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Official URL:https://doi.org/10.1101/gad.557910
PubMed:View item in PubMed
Creators Name:Wethmar, K. and Begay, V. and Smink, J.J. and Zaragoza, K. and Wiesenthal, V. and Doerken, B. and Calkhoven, C.F. and Leutz, A.
Journal Title:Genes & Development
Journal Abbreviation:Genes Dev
Volume:24
Number:1
Page Range:15-20
Date:1 January 2010
Keywords:Upstream ORF, Translational Control, C/EBPbeta, Liver Regeneration, Cell Cycle, Animals, Mice
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.
ISSN:0890-9369
Publisher:Cold Spring Harbor Laboratory Press (U.S.A.)
Item Type:Article

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