USP16 is an ISG15 cross-reactive deubiquitinase that targets pro-ISG15 and ISGylated proteins involved in metabolism
Interferon-induced ubiquitin (Ub)-like modifier ISG15 covalently modifies host and viral proteins to restrict viral infections. Its function is counteracted by the canonical deISGylase USP18 or Ub-specific protease 18. Notwithstanding indications for the existence of other ISG15 cross-reactive proteases, these remain to be identified. Here, we identify deubiquitinase USP16 as an ISG15 cross-reactive protease by means of ISG15 activity-based profiling. Recombinant USP16 cleaved pro-ISG15 and ISG15 isopeptide-linked model substrates in vitro, as well as ISGylated substrates from cell lysates. Moreover, interferon-induced stimulation of ISGylation was increased by depletion of USP16. The USP16-dependent ISG15 interactome indicated that the deISGylating function of USP16 may regulate metabolic pathways. Targeted enzymes include malate dehydrogenase, cytoplasmic superoxide dismutase 1, fructose-bisphosphate aldolase A, and cytoplasmic glutamic-oxaloacetic transaminase 1. USP16 may thus contribute to the regulation of a subset of metabolism-related proteins during type-I interferon responses.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:120 |
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| Enthalten in: |
Proceedings of the National Academy of Sciences of the United States of America - 120(2023), 50 vom: 12. Dez., Seite e2315163120 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Gan, Jin [VerfasserIn] |
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| Links: |
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| Themen: |
Activity-based probe |
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| Anmerkungen: |
Date Completed 11.12.2023 Date Revised 20.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1073/pnas.2315163120 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM365466565 |
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| 100 | 1 | |a Gan, Jin |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a USP16 is an ISG15 cross-reactive deubiquitinase that targets pro-ISG15 and ISGylated proteins involved in metabolism |
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| 500 | |a Date Revised 20.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Interferon-induced ubiquitin (Ub)-like modifier ISG15 covalently modifies host and viral proteins to restrict viral infections. Its function is counteracted by the canonical deISGylase USP18 or Ub-specific protease 18. Notwithstanding indications for the existence of other ISG15 cross-reactive proteases, these remain to be identified. Here, we identify deubiquitinase USP16 as an ISG15 cross-reactive protease by means of ISG15 activity-based profiling. Recombinant USP16 cleaved pro-ISG15 and ISG15 isopeptide-linked model substrates in vitro, as well as ISGylated substrates from cell lysates. Moreover, interferon-induced stimulation of ISGylation was increased by depletion of USP16. The USP16-dependent ISG15 interactome indicated that the deISGylating function of USP16 may regulate metabolic pathways. Targeted enzymes include malate dehydrogenase, cytoplasmic superoxide dismutase 1, fructose-bisphosphate aldolase A, and cytoplasmic glutamic-oxaloacetic transaminase 1. USP16 may thus contribute to the regulation of a subset of metabolism-related proteins during type-I interferon responses | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a ISG15 | |
| 650 | 4 | |a ISGylation | |
| 650 | 4 | |a USP16 | |
| 650 | 4 | |a activity-based probe | |
| 650 | 4 | |a metabolism | |
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| 650 | 7 | |a Ubiquitins |2 NLM | |
| 650 | 7 | |a Endopeptidases |2 NLM | |
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| 650 | 7 | |a Interferon Type I |2 NLM | |
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| 700 | 1 | |a Pinto-Fernández, Adán |e verfasserin |4 aut | |
| 700 | 1 | |a Flierman, Dennis |e verfasserin |4 aut | |
| 700 | 1 | |a Akkermans, Jimmy J L L |e verfasserin |4 aut | |
| 700 | 1 | |a O'Brien, Darragh P |e verfasserin |4 aut | |
| 700 | 1 | |a Greenwood, Helene |e verfasserin |4 aut | |
| 700 | 1 | |a Scott, Hannah Claire |e verfasserin |4 aut | |
| 700 | 1 | |a Fritz, Günter |e verfasserin |4 aut | |
| 700 | 1 | |a Knobeloch, Klaus-Peter |e verfasserin |4 aut | |
| 700 | 1 | |a Neefjes, Jacques |e verfasserin |4 aut | |
| 700 | 1 | |a van Dam, Hans |e verfasserin |4 aut | |
| 700 | 1 | |a Ovaa, Huib |e verfasserin |4 aut | |
| 700 | 1 | |a Ploegh, Hidde L |e verfasserin |4 aut | |
| 700 | 1 | |a Kessler, Benedikt M |e verfasserin |4 aut | |
| 700 | 1 | |a Geurink, Paul P |e verfasserin |4 aut | |
| 700 | 1 | |a Sapmaz, Aysegul |e verfasserin |4 aut | |
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