Broad and diverse mechanisms used by deubiquitinase family members in regulating the type I interferon signaling pathway during antiviral responses
Liu, Q., Wu, Y., Qin, Y., Hu, J., Xie, W., Qin, F. X.-F., Cui, J.
American Association for the Advancement of Science (AAAS)
Published 2018
American Association for the Advancement of Science (AAAS)
Published 2018
| Publication Date: |
2018-05-03
|
|---|---|
| Publisher: |
American Association for the Advancement of Science (AAAS)
|
| Electronic ISSN: |
2375-2548
|
| Topics: |
Natural Sciences in General
|
| Published by: |
| _version_ | 1836398917019762688 |
|---|---|
| autor | Liu, Q., Wu, Y., Qin, Y., Hu, J., Xie, W., Qin, F. X.-F., Cui, J. |
| beschreibung | The innate immune response conferred by type I interferons is essential for host defense against viral infection but needs to be tightly controlled to avoid immunopathology. We performed a systematic functional screening by CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9) knockout and overexpression to investigate the roles of the deubiquitinating enzyme (DUB) family in regulating antiviral immunity. We demonstrated that the expression of a large fraction of DUBs underwent complex temporal alteration, suggesting a dynamic program of feedback regulation. Moreover, we identified previously unrecognized roles of a subset of DUBs, including USP5, USP14, USP22, USP48, USP52, COPS5, and BRCC3, in inhibiting antiviral immunity at various levels. We explored an unexpected mechanism where multiple DUBs, such as USP5 and USP22, form diverse signalosomes with E3 ligases or DUBs to alter the substrates’ ubiquitination state instead of directly cleaving the ubiquitin chains on substrates via their protease activity. Altogether, our study has revealed a panoramic view of the broad and dynamic involvement of DUB family proteins in regulating antiviral responses. |
| citation_standardnr | 6250291 |
| datenlieferant | ipn_articles |
| feed_id | 228416 |
| feed_publisher | American Association for the Advancement of Science (AAAS) |
| feed_publisher_url | http://www.aaas.org/ |
| insertion_date | 2018-05-03 |
| journaleissn | 2375-2548 |
| publikationsjahr_anzeige | 2018 |
| publikationsjahr_facette | 2018 |
| publikationsjahr_intervall | 7984:2015-2019 |
| publikationsjahr_sort | 2018 |
| publisher | American Association for the Advancement of Science (AAAS) |
| quelle | Science Advances |
| relation | http://advances.sciencemag.org/cgi/content/short/4/5/eaar2824?rss=1 |
| search_space | articles |
| shingle_author_1 | Liu, Q., Wu, Y., Qin, Y., Hu, J., Xie, W., Qin, F. X.-F., Cui, J. |
| shingle_author_2 | Liu, Q., Wu, Y., Qin, Y., Hu, J., Xie, W., Qin, F. X.-F., Cui, J. |
| shingle_author_3 | Liu, Q., Wu, Y., Qin, Y., Hu, J., Xie, W., Qin, F. X.-F., Cui, J. |
| shingle_author_4 | Liu, Q., Wu, Y., Qin, Y., Hu, J., Xie, W., Qin, F. X.-F., Cui, J. |
| shingle_catch_all_1 | Broad and diverse mechanisms used by deubiquitinase family members in regulating the type I interferon signaling pathway during antiviral responses The innate immune response conferred by type I interferons is essential for host defense against viral infection but needs to be tightly controlled to avoid immunopathology. We performed a systematic functional screening by CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9) knockout and overexpression to investigate the roles of the deubiquitinating enzyme (DUB) family in regulating antiviral immunity. We demonstrated that the expression of a large fraction of DUBs underwent complex temporal alteration, suggesting a dynamic program of feedback regulation. Moreover, we identified previously unrecognized roles of a subset of DUBs, including USP5, USP14, USP22, USP48, USP52, COPS5, and BRCC3, in inhibiting antiviral immunity at various levels. We explored an unexpected mechanism where multiple DUBs, such as USP5 and USP22, form diverse signalosomes with E3 ligases or DUBs to alter the substrates’ ubiquitination state instead of directly cleaving the ubiquitin chains on substrates via their protease activity. Altogether, our study has revealed a panoramic view of the broad and dynamic involvement of DUB family proteins in regulating antiviral responses. Liu, Q., Wu, Y., Qin, Y., Hu, J., Xie, W., Qin, F. X.-F., Cui, J. American Association for the Advancement of Science (AAAS) 2375-2548 23752548 |
| shingle_catch_all_2 | Broad and diverse mechanisms used by deubiquitinase family members in regulating the type I interferon signaling pathway during antiviral responses The innate immune response conferred by type I interferons is essential for host defense against viral infection but needs to be tightly controlled to avoid immunopathology. We performed a systematic functional screening by CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9) knockout and overexpression to investigate the roles of the deubiquitinating enzyme (DUB) family in regulating antiviral immunity. We demonstrated that the expression of a large fraction of DUBs underwent complex temporal alteration, suggesting a dynamic program of feedback regulation. Moreover, we identified previously unrecognized roles of a subset of DUBs, including USP5, USP14, USP22, USP48, USP52, COPS5, and BRCC3, in inhibiting antiviral immunity at various levels. We explored an unexpected mechanism where multiple DUBs, such as USP5 and USP22, form diverse signalosomes with E3 ligases or DUBs to alter the substrates’ ubiquitination state instead of directly cleaving the ubiquitin chains on substrates via their protease activity. Altogether, our study has revealed a panoramic view of the broad and dynamic involvement of DUB family proteins in regulating antiviral responses. Liu, Q., Wu, Y., Qin, Y., Hu, J., Xie, W., Qin, F. X.-F., Cui, J. American Association for the Advancement of Science (AAAS) 2375-2548 23752548 |
| shingle_catch_all_3 | Broad and diverse mechanisms used by deubiquitinase family members in regulating the type I interferon signaling pathway during antiviral responses The innate immune response conferred by type I interferons is essential for host defense against viral infection but needs to be tightly controlled to avoid immunopathology. We performed a systematic functional screening by CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9) knockout and overexpression to investigate the roles of the deubiquitinating enzyme (DUB) family in regulating antiviral immunity. We demonstrated that the expression of a large fraction of DUBs underwent complex temporal alteration, suggesting a dynamic program of feedback regulation. Moreover, we identified previously unrecognized roles of a subset of DUBs, including USP5, USP14, USP22, USP48, USP52, COPS5, and BRCC3, in inhibiting antiviral immunity at various levels. We explored an unexpected mechanism where multiple DUBs, such as USP5 and USP22, form diverse signalosomes with E3 ligases or DUBs to alter the substrates’ ubiquitination state instead of directly cleaving the ubiquitin chains on substrates via their protease activity. Altogether, our study has revealed a panoramic view of the broad and dynamic involvement of DUB family proteins in regulating antiviral responses. Liu, Q., Wu, Y., Qin, Y., Hu, J., Xie, W., Qin, F. X.-F., Cui, J. American Association for the Advancement of Science (AAAS) 2375-2548 23752548 |
| shingle_catch_all_4 | Broad and diverse mechanisms used by deubiquitinase family members in regulating the type I interferon signaling pathway during antiviral responses The innate immune response conferred by type I interferons is essential for host defense against viral infection but needs to be tightly controlled to avoid immunopathology. We performed a systematic functional screening by CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9) knockout and overexpression to investigate the roles of the deubiquitinating enzyme (DUB) family in regulating antiviral immunity. We demonstrated that the expression of a large fraction of DUBs underwent complex temporal alteration, suggesting a dynamic program of feedback regulation. Moreover, we identified previously unrecognized roles of a subset of DUBs, including USP5, USP14, USP22, USP48, USP52, COPS5, and BRCC3, in inhibiting antiviral immunity at various levels. We explored an unexpected mechanism where multiple DUBs, such as USP5 and USP22, form diverse signalosomes with E3 ligases or DUBs to alter the substrates’ ubiquitination state instead of directly cleaving the ubiquitin chains on substrates via their protease activity. Altogether, our study has revealed a panoramic view of the broad and dynamic involvement of DUB family proteins in regulating antiviral responses. Liu, Q., Wu, Y., Qin, Y., Hu, J., Xie, W., Qin, F. X.-F., Cui, J. American Association for the Advancement of Science (AAAS) 2375-2548 23752548 |
| shingle_title_1 | Broad and diverse mechanisms used by deubiquitinase family members in regulating the type I interferon signaling pathway during antiviral responses |
| shingle_title_2 | Broad and diverse mechanisms used by deubiquitinase family members in regulating the type I interferon signaling pathway during antiviral responses |
| shingle_title_3 | Broad and diverse mechanisms used by deubiquitinase family members in regulating the type I interferon signaling pathway during antiviral responses |
| shingle_title_4 | Broad and diverse mechanisms used by deubiquitinase family members in regulating the type I interferon signaling pathway during antiviral responses |
| timestamp | 2025-06-30T23:34:41.763Z |
| titel | Broad and diverse mechanisms used by deubiquitinase family members in regulating the type I interferon signaling pathway during antiviral responses |
| titel_suche | Broad and diverse mechanisms used by deubiquitinase family members in regulating the type I interferon signaling pathway during antiviral responses |
| topic | TA-TD |
| uid | ipn_articles_6250291 |