Negative Regulation of the Innate Immune Response through Proteasomal Degradation and Deubiquitination
The rapid and dynamic activation of the innate immune system is achieved through complex signaling networks regulated by post-translational modifications modulating the subcellular localization, activity, and abundance of signaling molecules. Many constitutively expressed signaling molecules are pre...
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MDPI AG
2021-03-01
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Online Access: | https://www.mdpi.com/1999-4915/13/4/584 |
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author | Valentina Budroni Gijs A. Versteeg |
author_facet | Valentina Budroni Gijs A. Versteeg |
author_sort | Valentina Budroni |
collection | DOAJ |
description | The rapid and dynamic activation of the innate immune system is achieved through complex signaling networks regulated by post-translational modifications modulating the subcellular localization, activity, and abundance of signaling molecules. Many constitutively expressed signaling molecules are present in the cell in inactive forms, and become functionally activated once they are modified with ubiquitin, and, in turn, inactivated by removal of the same post-translational mark. Moreover, upon infection resolution a rapid remodeling of the proteome needs to occur, ensuring the removal of induced response proteins to prevent hyperactivation. This review discusses the current knowledge on the negative regulation of innate immune signaling pathways by deubiquitinating enzymes, and through degradative ubiquitination. It focusses on spatiotemporal regulation of deubiquitinase and E3 ligase activities, mechanisms for re-establishing proteostasis, and degradation through immune-specific feedback mechanisms vs. general protein quality control pathways. |
first_indexed | 2024-03-10T12:45:35Z |
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id | doaj.art-751113f2102843aa8a7984f6cf4b86be |
institution | Directory Open Access Journal |
issn | 1999-4915 |
language | English |
last_indexed | 2024-03-10T12:45:35Z |
publishDate | 2021-03-01 |
publisher | MDPI AG |
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series | Viruses |
spelling | doaj.art-751113f2102843aa8a7984f6cf4b86be2023-11-21T13:30:21ZengMDPI AGViruses1999-49152021-03-0113458410.3390/v13040584Negative Regulation of the Innate Immune Response through Proteasomal Degradation and DeubiquitinationValentina Budroni0Gijs A. Versteeg1Max Perutz Labs, Department of Microbiology, Immunobiology, and Genetics, University of Vienna, Vienna Biocenter (VBC), 1030 Vienna, AustriaMax Perutz Labs, Department of Microbiology, Immunobiology, and Genetics, University of Vienna, Vienna Biocenter (VBC), 1030 Vienna, AustriaThe rapid and dynamic activation of the innate immune system is achieved through complex signaling networks regulated by post-translational modifications modulating the subcellular localization, activity, and abundance of signaling molecules. Many constitutively expressed signaling molecules are present in the cell in inactive forms, and become functionally activated once they are modified with ubiquitin, and, in turn, inactivated by removal of the same post-translational mark. Moreover, upon infection resolution a rapid remodeling of the proteome needs to occur, ensuring the removal of induced response proteins to prevent hyperactivation. This review discusses the current knowledge on the negative regulation of innate immune signaling pathways by deubiquitinating enzymes, and through degradative ubiquitination. It focusses on spatiotemporal regulation of deubiquitinase and E3 ligase activities, mechanisms for re-establishing proteostasis, and degradation through immune-specific feedback mechanisms vs. general protein quality control pathways.https://www.mdpi.com/1999-4915/13/4/584ubiquitindeubiquitinaseE3 ligaseinnate immune systemproteasomecytokine |
spellingShingle | Valentina Budroni Gijs A. Versteeg Negative Regulation of the Innate Immune Response through Proteasomal Degradation and Deubiquitination Viruses ubiquitin deubiquitinase E3 ligase innate immune system proteasome cytokine |
title | Negative Regulation of the Innate Immune Response through Proteasomal Degradation and Deubiquitination |
title_full | Negative Regulation of the Innate Immune Response through Proteasomal Degradation and Deubiquitination |
title_fullStr | Negative Regulation of the Innate Immune Response through Proteasomal Degradation and Deubiquitination |
title_full_unstemmed | Negative Regulation of the Innate Immune Response through Proteasomal Degradation and Deubiquitination |
title_short | Negative Regulation of the Innate Immune Response through Proteasomal Degradation and Deubiquitination |
title_sort | negative regulation of the innate immune response through proteasomal degradation and deubiquitination |
topic | ubiquitin deubiquitinase E3 ligase innate immune system proteasome cytokine |
url | https://www.mdpi.com/1999-4915/13/4/584 |
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