IFN-γ-inducible antiviral responses require ULK1-mediated activation of MLK3 and ERK5
| Autor: | Mariafausta Fischietti, Eleanor N. Fish, Patrick A. Ozark, Gavin T. Blyth, Leonidas C. Platanias, Neha K. Reddy, Diana Saleiro, Roger J. Davis, Curt M. Horvath, Ewa M. Kosciuczuk, Beata Majchrzak-Kita, Ahmet Dirim Arslan |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Transcription Genetic Biochemistry Article 03 medical and health sciences Interferon-gamma Mice 0302 clinical medicine Interferon Cell Line Tumor medicine Autophagy Animals Autophagy-Related Protein-1 Homolog Humans STAT1 Phosphorylation Protein kinase A Molecular Biology Transcription factor Mitogen-Activated Protein Kinase 7 Receptors Interferon biology Kinase Chemistry Gene Expression Profiling Intracellular Signaling Peptides and Proteins Cell Biology U937 Cells ULK1 MAP Kinase Kinase Kinases Class III Phosphatidylinositol 3-Kinases Immunity Innate Recombinant Proteins Cell biology 030104 developmental biology Virus Diseases Multigene Family biology.protein STAT protein Cytokines Beclin-1 Signal transduction 030215 immunology medicine.drug Protein Binding Signal Transduction |
| Zdroj: | Science signaling. 11(557) |
| ISSN: | 1937-9145 |
| Popis: | It is well established that activation of the transcription factor signal transducer and activator of transcription 1 (STAT1) is required for the interferon-γ (IFN-γ)-mediated antiviral response. Here, we found that IFN-γ receptor stimulation also activated Unc-51-like kinase 1 (ULK1), an initiator of Beclin-1-mediated autophagy. Furthermore, the interaction between ULK1 and the mitogen-activated protein kinase kinase kinase MLK3 (mixed lineage kinase 3) was necessary for MLK3 phosphorylation and downstream activation of the kinase ERK5. This autophagy-independent activity of ULK1 promoted the transcription of key antiviral IFN-stimulated genes (ISGs) and was essential for IFN-γ-dependent antiviral effects. These findings define a previously unknown IFN-γ pathway that appears to be a key element of the antiviral response. |
| Databáze: | OpenAIRE |
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