Human Gene Set: COLINA_TARGETS_OF_4EBP1_AND_4EBP2


Standard name COLINA_TARGETS_OF_4EBP1_AND_4EBP2
Systematic name M1919
Brief description Genes up-regulated in MEF cells (embryonic fibroblast) with double knockout of the translation repressors 4EBP1 [GeneID=1978] and 4EBP2 [GeneID=1979].
Full description or abstract Transcriptional activation of cytokines, such as type-I interferons (interferon (IFN)-alpha and IFN-beta), constitutes the first line of antiviral defence. Here we show that translational control is critical for induction of type-I IFN production. In mouse embryonic fibroblasts lacking the translational repressors 4E-BP1 and 4E-BP2, the threshold for eliciting type-I IFN production is lowered. Consequently, replication of encephalomyocarditis virus, vesicular stomatitis virus, influenza virus and Sindbis virus is markedly suppressed. Furthermore, mice with both 4E- and 4E-BP2 genes (also known as Eif4ebp1 and Eif4ebp2, respectively) knocked out are resistant to vesicular stomatitis virus infection, and this correlates with an enhanced type-I IFN production in plasmacytoid dendritic cells and the expression of IFN-regulated genes in the lungs. The enhanced type-I IFN response in 4E-BP1-/- 4E-BP2-/- double knockout mouse embryonic fibroblasts is caused by upregulation of interferon regulatory factor 7 (Irf7) messenger RNA translation. These findings highlight the role of 4E-BPs as negative regulators of type-I IFN production, via translational repression of Irf7 mRNA.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 18272964   Authors: Colina R,Costa-Mattioli M,Dowling RJ,Jaramillo M,Tai LH,Breitbach CJ,Martineau Y,Larsson O,Rong L,Svitkin YV,Makrigiannis AP,Bell JC,Sonenberg N
Exact source Supplementary Fig. 7C
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Source species Mus musculus
Contributed by Jessica Robertson (MSigDB Team)
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identifier namespace		 Mouse_NCBI_Gene_ID
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Version history 3.1: First introduced


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