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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Main Authors: Valentina Budroni, Gijs A. Versteeg
Format: Article
Language:English
Published: MDPI AG 2021-03-01
Series:Viruses
Subjects:
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.
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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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