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Start Over Author "Caroline Asselman" Topic proteomics
2 results on '"Caroline Asselman"'

1. Proteome Profiling of RNF213 Depleted Cells Reveals Nitric Oxide Regulator DDAH1 Antilisterial Activity

Author

Lia Martina, Caroline Asselman, Fabien Thery, Katie Boucher, Louis Delhaye, Teresa M. Maia, Bart Dermaut, Sven Eyckerman, and Francis Impens

Subjects
Listeria, bacterial infection, Moyamoya, nitric oxide, NO, mass spectrometry, proteomics, Microbiology, QR1-502
Abstract

RNF213 is a large, poorly characterized interferon-induced protein. Mutations in RNF213 are associated with predisposition for Moyamoya disease (MMD), a rare cerebrovascular disorder. Recently, RNF213 was found to have broad antimicrobial activity in vitro and in vivo, yet the molecular mechanisms behind this function remain unclear. Using mass spectrometry-based proteomics and validation by real-time PCR we report here that knockdown of RNF213 leads to transcriptional upregulation of MVP and downregulation of CYR61, in line with reported pro- and anti-bacterial activities of these proteins. Knockdown of RNF213 also results in downregulation of DDAH1, which we discover to exert antimicrobial activity against Listeria monocytogenes infection. DDAH1 regulates production of nitric oxide (NO), a molecule with both vascular and antimicrobial effects. We show that NO production is reduced in macrophages from RNF213 KO mice, suggesting that RNF213 controls Listeria infection through regulation of DDAH1 transcription and production of NO. Our findings propose a potential mechanism for the antilisterial activity of RNF213 and highlight NO as a potential link between RNF213-mediated immune responses and the development of MMD.

Published
2021
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2. Ring finger protein 213 assembles into a sensor for ISGylated proteins with antimicrobial activity

Author

Caroline Asselman, Madeleine Vessely, Katie Boucher, George D. Moschonas, Koen Sedeyn, Francis Impens, Denzel Eggermont, Tino Hochepied, Qi Wen Teo, Xavier Saelens, Lilliana Radoshevich, Jingshu Zhang, Clara Bredow, Bart Dermaut, Klaus-Peter Knobeloch, Sven Eyckerman, Lia Martina, Sumana Sanyal, Nico Callewaert, Antje Beling, Yifeng Zhang, Heidi Repo, Delphine De Sutter, Fabien Thery, Nele Festjens, and Kevin Leandro

Subjects
Male, Proteomics, ISG15, THP-1 Cells, General Physics and Astronomy, Herpesvirus 1, Human, medicine.disease_cause, Anti-Infective Agents, INTERFERON-STIMULATED GENE, Interferon, Lipid droplet, Medicine and Health Sciences, LISTERIA-MONOCYTOGENES, Enterovirus, LIGASE, Adenosine Triphosphatases, Multidisciplinary, Effector, Chemistry, HUMAN INTERACTOME, PAPAIN-LIKE PROTEASE, Cell biology, Mechanisms of disease, Interferon Type I, Small Ubiquitin-Related Modifier Proteins, Cytokines, VIRUS, AUTOPHAGY, MYCOBACTERIUM-TUBERCULOSIS, Ring Finger Protein 213, Protein Binding, medicine.drug, Listeria, Science, Ubiquitin-Protein Ligases, Article, General Biochemistry, Genetics and Molecular Biology, Virus, medicine, Animals, Humans, MOYAMOYA-DISEASE, Ubiquitins, Ubiquitin, Intracellular parasite, Cerebrovascular disorder, Biology and Life Sciences, Lipid Droplets, General Chemistry, Listeria monocytogenes, Mice, Inbred C57BL, HEK293 Cells, Herpes simplex virus, A549 Cells, Protein Multimerization, HeLa Cells, Post-translational modifications
Abstract

ISG15 is an interferon-stimulated, ubiquitin-like protein that can conjugate to substrate proteins (ISGylation) to counteract microbial infection, but the underlying mechanisms remain elusive. Here, we use a virus-like particle trapping technology to identify ISG15-binding proteins and discover Ring Finger Protein 213 (RNF213) as an ISG15 interactor and cellular sensor of ISGylated proteins. RNF213 is a poorly characterized, interferon-induced megaprotein that is frequently mutated in Moyamoya disease, a rare cerebrovascular disorder. We report that interferon induces ISGylation and oligomerization of RNF213 on lipid droplets, where it acts as a sensor for ISGylated proteins. We show that RNF213 has broad antimicrobial activity in vitro and in vivo, counteracting infection with Listeria monocytogenes, herpes simplex virus 1, human respiratory syncytial virus and coxsackievirus B3, and we observe a striking co-localization of RNF213 with intracellular bacteria. Together, our findings provide molecular insights into the ISGylation pathway and reveal RNF213 as a key antimicrobial effector., During microbial infection, proteins are modified by the ubiquitin-like protein ISG15. Here, the authors uncover RNF213 as a sensor for ISGylated proteins on the surface of lipid droplets, showing that RNF213 has antiviral properties but also directly targets intracellular bacteria in infected cells.

Published
2021

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