| First Author | Muendlein HI | Year | 2020 |
| Journal | Cell Rep | Volume | 30 |
| Issue | 3 | Pages | 699-713.e4 |
| PubMed ID | 31968247 | Mgi Jnum | J:288086 |
| Mgi Id | MGI:6415897 | Doi | 10.1016/j.celrep.2019.12.073 |
| Citation | Muendlein HI, et al. (2020) Constitutive Interferon Attenuates RIPK1/3-Mediated Cytokine Translation. Cell Rep 30(3):699-713.e4 |
| abstractText | 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. |
