Constitutive Interferon Attenuates RIPK1/3-Mediated Cytokine Translation
| Autor: | Vladimir Ilyukha, Alexei Degterev, Wilson M. Connolly, Hayley I. Muendlein, Beiyun C. Liu, Nahum Sonenberg, Jodie R. Pietruska, Alexander Poltorak, Stephen A Schworer, Amy Y. Tang, Irina Smirnova, Joseph Sarhan, Soroush Tahmasebi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Lipopolysaccharides medicine.medical_treatment Necroptosis Down-Regulation Cell Cycle Proteins mTORC1 Biology Mechanistic Target of Rapamycin Complex 1 General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences RIPK1 0302 clinical medicine medicine Animals Humans RNA Messenger Kinase activity Protein kinase A Protein kinase B lcsh:QH301-705.5 Adaptor Proteins Signal Transducing Inflammation EIF4E Macrophage Activation Cell biology Mice Inbred C57BL 030104 developmental biology Cytokine Eukaryotic Initiation Factor-4E lcsh:Biology (General) Protein Biosynthesis Receptor-Interacting Protein Serine-Threonine Kinases Cytokines Female Interferons 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Cell Reports, Vol 30, Iss 3, Pp 699-713.e4 (2020) Cell reports |
| ISSN: | 2211-1247 |
| Popis: | SUMMARY Receptor-interacting protein kinase 1 (RIPK1) and 3 (RIPK3) are well known for their capacity to drive necroptosis via mixed-lineage kinase-like domain (MLKL). Recently, RIPK1/3 kinase activity has been shown to drive inflammation via activation of MAPK signaling. However, the regulatory mechanisms underlying this kinase-dependent cytokine production remain poorly understood. In the present study, we establish that the kinase activity of RIPK1/3 regulates cytokine translation in mouse and human macrophages. Furthermore, we show that this inflammatory response is downregulated by type I interferon (IFN) signaling, independent of type I IFN-promoted cell death. Specifically, low-level constitutive IFN signaling attenuates RIPK-driven activation of cap-dependent translation initiation pathway components AKT, mTORC1, 4E-BP and eIF4E, while promoting RIPK-dependent cell death. Altogether, these data characterize constitutive IFN signaling as a regulator of RIPK-dependent inflammation and establish cap-dependent translation as a crucial checkpoint in the regulation of cytokine production. In Brief Balancing inflammatory responses is critical for host survival. Muendlein et al. show that constitutive type I IFN signaling inhibits translation machinery activated downstream of the kinase activity of RIPK1/3, preventing the production of a subset of inflammatory cytokines. This work identifies cap-dependent translation as a checkpoint in regulation of RIPK1/3-kinase-dependent inflammation. Graphical Abstract |
| Databáze: | OpenAIRE |
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