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 prote...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
National Academy of Sciences
2023
|
| _version_ | 1826311751151386624 |
|---|---|
| author | Gan, J Pinto-Fernández, A Flierman, D Akkermans, JJLL O'Brien, DP Greenwood, H Scott, HC Fritz, G Knobeloch, K-P Neefjes, J van Dam, H Ovaa, H Ploegh, HL Kessler, BM Geurink, PP Sapmaz, A |
| author_facet | Gan, J Pinto-Fernández, A Flierman, D Akkermans, JJLL O'Brien, DP Greenwood, H Scott, HC Fritz, G Knobeloch, K-P Neefjes, J van Dam, H Ovaa, H Ploegh, HL Kessler, BM Geurink, PP Sapmaz, A |
| author_sort | Gan, J |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T08:14:18Z |
| format | Journal article |
| id | oxford-uuid:96f70c19-cf43-487d-a8f8-81a302e121ac |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T08:14:18Z |
| publishDate | 2023 |
| publisher | National Academy of Sciences |
| record_format | dspace |
| spelling | oxford-uuid:96f70c19-cf43-487d-a8f8-81a302e121ac2023-12-18T06:45:45ZUSP16 is an ISG15 cross-reactive deubiquitinase that targets pro-ISG15 and ISGylated proteins involved in metabolismJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:96f70c19-cf43-487d-a8f8-81a302e121acEnglishSymplectic ElementsNational Academy of Sciences2023Gan, JPinto-Fernández, AFlierman, DAkkermans, JJLLO'Brien, DPGreenwood, HScott, HCFritz, GKnobeloch, K-PNeefjes, Jvan Dam, HOvaa, HPloegh, HLKessler, BMGeurink, PPSapmaz, AInterferon-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. |
| spellingShingle | Gan, J Pinto-Fernández, A Flierman, D Akkermans, JJLL O'Brien, DP Greenwood, H Scott, HC Fritz, G Knobeloch, K-P Neefjes, J van Dam, H Ovaa, H Ploegh, HL Kessler, BM Geurink, PP Sapmaz, A USP16 is an ISG15 cross-reactive deubiquitinase that targets pro-ISG15 and ISGylated proteins involved in metabolism |
| title | USP16 is an ISG15 cross-reactive deubiquitinase that targets pro-ISG15 and ISGylated proteins involved in metabolism |
| title_full | USP16 is an ISG15 cross-reactive deubiquitinase that targets pro-ISG15 and ISGylated proteins involved in metabolism |
| title_fullStr | USP16 is an ISG15 cross-reactive deubiquitinase that targets pro-ISG15 and ISGylated proteins involved in metabolism |
| title_full_unstemmed | USP16 is an ISG15 cross-reactive deubiquitinase that targets pro-ISG15 and ISGylated proteins involved in metabolism |
| title_short | USP16 is an ISG15 cross-reactive deubiquitinase that targets pro-ISG15 and ISGylated proteins involved in metabolism |
| title_sort | usp16 is an isg15 cross reactive deubiquitinase that targets pro isg15 and isgylated proteins involved in metabolism |
| work_keys_str_mv | AT ganj usp16isanisg15crossreactivedeubiquitinasethattargetsproisg15andisgylatedproteinsinvolvedinmetabolism AT pintofernandeza usp16isanisg15crossreactivedeubiquitinasethattargetsproisg15andisgylatedproteinsinvolvedinmetabolism AT fliermand usp16isanisg15crossreactivedeubiquitinasethattargetsproisg15andisgylatedproteinsinvolvedinmetabolism AT akkermansjjll usp16isanisg15crossreactivedeubiquitinasethattargetsproisg15andisgylatedproteinsinvolvedinmetabolism AT obriendp usp16isanisg15crossreactivedeubiquitinasethattargetsproisg15andisgylatedproteinsinvolvedinmetabolism AT greenwoodh usp16isanisg15crossreactivedeubiquitinasethattargetsproisg15andisgylatedproteinsinvolvedinmetabolism AT scotthc usp16isanisg15crossreactivedeubiquitinasethattargetsproisg15andisgylatedproteinsinvolvedinmetabolism AT fritzg usp16isanisg15crossreactivedeubiquitinasethattargetsproisg15andisgylatedproteinsinvolvedinmetabolism AT knobelochkp usp16isanisg15crossreactivedeubiquitinasethattargetsproisg15andisgylatedproteinsinvolvedinmetabolism AT neefjesj usp16isanisg15crossreactivedeubiquitinasethattargetsproisg15andisgylatedproteinsinvolvedinmetabolism AT vandamh usp16isanisg15crossreactivedeubiquitinasethattargetsproisg15andisgylatedproteinsinvolvedinmetabolism AT ovaah usp16isanisg15crossreactivedeubiquitinasethattargetsproisg15andisgylatedproteinsinvolvedinmetabolism AT ploeghhl usp16isanisg15crossreactivedeubiquitinasethattargetsproisg15andisgylatedproteinsinvolvedinmetabolism AT kesslerbm usp16isanisg15crossreactivedeubiquitinasethattargetsproisg15andisgylatedproteinsinvolvedinmetabolism AT geurinkpp usp16isanisg15crossreactivedeubiquitinasethattargetsproisg15andisgylatedproteinsinvolvedinmetabolism AT sapmaza usp16isanisg15crossreactivedeubiquitinasethattargetsproisg15andisgylatedproteinsinvolvedinmetabolism |