The in vivo ISGylome links ISG15 to metabolic pathways and autophagy upon Listeria monocytogenes infection
| Autor: | Pascale Cossart, Olivier Dussurget, Kevin Leandro, Lilliana Radoshevich, Clara Bredow, Mariko Foecke, Daniel Jiménez-Fernández, Nicholas C. Wu, Yifeng Zhang, Emma K. Luhmann, Fabien Thery, Antje Beling, Francis Impens, Klaus-Peter Knobeloch |
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| Přispěvatelé: | Carver College of Medicine, University of Iowa, VIB-UGent Center for Medical Biotechnology, Department for Biomolecular Medicine, Universiteit Gent = Ghent University (UGENT), Department of Integrative Structural and Computational Biology [La Jolla, CA, USA], The Scripps Research Institute [La Jolla, San Diego], Interactions Bactéries-Cellules (UIBC), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Berlin Institute of Health (BIH), Institute of Neuropathology, University of Freiburg [Freiburg], VIB Center for Medical Biotechnology, Universiteit Gent = Ghent University [Belgium] (UGENT), Scripps Research Institute, Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Lallemant, Pascal |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Proteomics
0301 basic medicine [SDV]Life Sciences [q-bio] General Physics and Astronomy ns1 protein 0302 clinical medicine Medicine and Health Sciences Listeriosis lcsh:Science Multidisciplinary TOR Serine-Threonine Kinases Acetylation Bacterial host response ANTIVIRAL MOLECULE 3. Good health Cell biology [SDV] Life Sciences [q-bio] secretion Liver INFLUENZA NS1 PROTEIN Cytokines targets SECRETION Infection influenza Metabolic Networks and Pathways complex conjugation Science Quantitative proteomics Genetics and Molecular Biology Biology Article General Biochemistry Genetics and Molecular Biology proteome-wide identification Mitochondrial Proteins stimulated gene-15 03 medical and health sciences Downregulation and upregulation TARGETS Autophagy Animals Secretion Ubiquitins PI3K/AKT/mTOR pathway STIMULATED GENE-15 antiviral molecule PROTEOME-WIDE IDENTIFICATION COMPLEX Lysine Ubiquitination ISGYLATION General Chemistry Listeria monocytogenes ISG15 Mice Mutant Strains Mice Inbred C57BL Metabolic pathway 030104 developmental biology isgylation CONJUGATION General Biochemistry lcsh:Q Protein Processing Post-Translational 030217 neurology & neurosurgery Post-translational modifications |
| Zdroj: | NATURE COMMUNICATIONS Nature Communications Nature Communications, 2019, 10 (1), pp.1-15. ⟨10.1038/s41467-019-13393-x⟩ Nature Communications, Vol 10, Iss 1, Pp 1-15 (2019) Nature Communications, Nature Publishing Group, 2019, 10 (1), pp.1-15. ⟨10.1038/s41467-019-13393-x⟩ |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-019-13393-x⟩ |
| Popis: | ISG15 is an interferon-stimulated, ubiquitin-like protein, with anti-viral and anti-bacterial activity. Here, we map the endogenous in vivo ISGylome in the liver following Listeria monocytogenes infection by combining murine models of reduced or enhanced ISGylation with quantitative proteomics. Our method identifies 930 ISG15 sites in 434 proteins and also detects changes in the host ubiquitylome. The ISGylated targets are enriched in proteins which alter cellular metabolic processes, including upstream modulators of the catabolic and antibacterial pathway of autophagy. Computational analysis of substrate structures reveals that a number of ISG15 modifications occur at catalytic sites or dimerization interfaces of enzymes. Finally, we demonstrate that animals and cells with enhanced ISGylation have increased basal and infection-induced autophagy through the modification of mTOR, WIPI2, AMBRA1, and RAB7. Taken together, these findings ascribe a role of ISGylation to temporally reprogram organismal metabolism following infection through direct modification of a subset of enzymes in the liver. ISG15 is a ubiquitin-like modifier that can be upregulated in response to bacterial infections. Here, the authors use proteomics to identify endogenous ISGylation substrates in the liver of Listeria monocytogenes infected mice and show that ISGylation alters basal and infection-induced autophagy. |
| Databáze: | OpenAIRE |
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