例如:"lncRNA", "apoptosis", "WRKY"

Constitutive Interferon Attenuates RIPK1/3-Mediated Cytokine Translation.

Cell Rep. 2020 Jan 21;30(3):699-713.e4
Hayley I Muendlein 1 , Joseph Sarhan 2 , Beiyun C Liu 3 , Wilson M Connolly 4 , Stephen A Schworer 5 , Irina Smirnova 4 , Amy Y Tang 4 , Vladimir Ilyukha 6 , Jodie Pietruska 7 , Soroush Tahmasebi 8 , Nahum Sonenberg 8 , Alexei Degterev 7 , Alexander Poltorak 9
Hayley I Muendlein 1 , Joseph Sarhan 2 , Beiyun C Liu 3 , Wilson M Connolly 4 , Stephen A Schworer 5 , Irina Smirnova 4 , Amy Y Tang 4 , Vladimir Ilyukha 6 , Jodie Pietruska 7 , Soroush Tahmasebi 8 , Nahum Sonenberg 8 , Alexei Degterev 7 , Alexander Poltorak 9
+ et al

[No authors listed]

Author information
  • 1 Graduate Program in Genetics, Tufts Graduate School of Biomedical Sciences, Boston, MA 02111, USA.
  • 2 Medical Scientist Training Program (MSTP), Tufts University School of Medicine, Boston, MA 02111, USA; Graduate Program in Immunology, Tufts Graduate School of Biomedical Sciences, Boston, MA 02111, USA.
  • 3 Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38104, USA.
  • 4 Department of Immunology, Tufts University School of Medicine, Boston, MA 02111, USA.
  • 5 Allergy and Immunology, University of North Carolina, Chapel Hill, NC 27599, USA.
  • 6 Petrozavodsk State University, Petrozavodsk, Republic of Karelia 185910, Russia.
  • 7 Department of Cell, Molecular & Developmental Biology, Tufts University School of Medicine, Boston, MA 02111, USA.
  • 8 Department of Biochemistry, Goodman Cancer Research Center McGill University, Montreal, QC H3A 1A3, Canada.
  • 9 Department of Immunology, Tufts University School of Medicine, Boston, MA 02111, USA; Petrozavodsk State University, Petrozavodsk, Republic of Karelia 185910, Russia. Electronic address: alexander.poltorak@tufts.edu.

摘要


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.

KEYWORDS: constitutive IFN, inflammation, macrophage, necroptosis, receptor-interacting protein kinases, translation