| Autor: |
Hayley I. Muendlein, Joseph Sarhan, Beiyun C. Liu, Wilson M. Connolly, Stephen A. Schworer, Irina Smirnova, Amy Y. Tang, Vladimir Ilyukha, Jodie Pietruska, Soroush Tahmasebi, Nahum Sonenberg, Alexei Degterev, Alexander Poltorak |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
|
| Zdroj: |
Cell Reports, Vol 30, Iss 3, Pp 699-713.e4 (2020) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2019.12.073 |
| 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. : 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. Keywords: inflammation, necroptosis, constitutive IFN, translation, macrophage, receptor-interacting protein kinases |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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