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Accession IconGSE18115

Dendritic cells and stress translation

Organism Icon Mus musculus
Sample Icon 8 Downloadable Samples
Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

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In response to inflammatory stimulation, dendritic cells (DCs) have a remarkable pattern of differentiation that exhibits specific mechanisms to control the immune response. Here we show that in response to polyriboinosinic:polyribocytidylic acid (poly I:C), DCs mount a specific transcription program during which the growth arrest and DNA damage-inducible protein 34 (GADD34/MyD116), a phosphatase 1 (PP1) cofactor, is expressed. Together with its constitutively active counterpart CReP, GADD34 promotes an extensive dephosphorylation of the translation initiation factor eIF2-alfa in activated DCs. In turn, dephosphorylation of eIF2-alfa prevents the translation inhibition normally associated with cellular stress or detection of cytoplasmic double-stranded RNA. These observations have important implications in linking pathogen detection with the integrated stress responses molecular machinery. The importance of this regulation for DC function is exemplified by the alteration of IFN-beta production or the induction of caspase-3 cleavage upon inhibition of PP1 activity.
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