Journal article
The in vivo ISGylome links ISG15 to metabolic pathways and autophagy upon Listeria monocytogenes infection
Nature communications, Vol.10(1), pp.5383-15
11/26/2019
DOI: 10.1038/s41467-019-13393-x
PMCID: PMC6879477
PMID: 31772204
Abstract
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.
Details
- Title: Subtitle
- The in vivo ISGylome links ISG15 to metabolic pathways and autophagy upon Listeria monocytogenes infection
- Creators
- Yifeng Zhang - Roy J. and Lucille A. Carver College of MedicineFabien Thery - VIB-UGent Center for Medical BiotechnologyNicholas C. Wu - Scripps Research InstituteEmma K. Luhmann - Roy J. and Lucille A. Carver College of MedicineOlivier Dussurget - Institut PasteurMariko Foecke - InsermClara Bredow - Humboldt-Universität zu BerlinDaniel Jimenez-Fernandez - Univ Freiburg, Inst Neuropathol, Med Fac, Freiburg, GermanyKevin Leandro - Ghent UniversityAntje Beling - Humboldt-Universität zu BerlinKlaus-Peter Knobeloch - University of FreiburgFrancis Impens - Ghent UniversityPascale Cossart - InsermLilliana Radoshevich - Roy J. and Lucille A. Carver College of Medicine
- Resource Type
- Journal article
- Publication Details
- Nature communications, Vol.10(1), pp.5383-15
- DOI
- 10.1038/s41467-019-13393-x
- PMID
- 31772204
- PMCID
- PMC6879477
- NLM abbreviation
- Nat Commun
- ISSN
- 2041-1723
- eISSN
- 2041-1723
- Publisher
- Springer Nature
- Number of pages
- 15
- Grant note
- Fondation le Roch les Mousquetaires ERANET Infect-ERA BacVIRISG15 BE 6335/6-1 / German Research Foundation; German Research Foundation (DFG) 670823 / European Research Council (ERC); European Commission International Max Planck Research School for Infectious Diseases and Immunology (IMPRS-IDI), Berlin Foundation for Experimental Biomedicine Zurich, Switzerland KN590/7-1 / DFG; German Research Foundation (DFG); European Commission G0F8616N / Research Foundation Flanders (FWO); FWO
- Language
- English
- Date published
- 11/26/2019
- Academic Unit
- Molecular Physiology and Biophysics; Microbiology and Immunology
- Record Identifier
- 9984297439602771
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