Negative Regulation of the Innate Immune Response Through Proteasomal Degradation and Deubiquitination

Overview

Journal Viruses

Publisher MDPI

Specialty Microbiology

Date 2021 Apr 3

PMID 33808506

Citations 6

Authors

Valentina Budroni

Gijs A Versteeg

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

The role of cGAS-STING pathway ubiquitination in innate immunity and multiple diseases.

Deng C, Chen D, Yang L, Zhang Y, Jin C, Li Y Front Immunol. 2025; 16:1522200.

PMID: 40028324 PMC: 11868049. DOI: 10.3389/fimmu.2025.1522200.

HCoV-229E Mpro Suppresses RLR-Mediated Innate Immune Signalling Through Cleavage of NEMO and Through Other Mechanisms.

Martianez-Vendrell X, van Kasteren P, Myeni S, Kikkert M Int J Mol Sci. 2025; 26(3).

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Regulation of inflammation and immunity in sepsis by E3 ligases.

Shao S, Zhou D, Feng J, Liu Y, Baturuhu , Yin H Front Endocrinol (Lausanne). 2023; 14:1124334.

PMID: 37465127 PMC: 10351979. DOI: 10.3389/fendo.2023.1124334.

Phase separation in innate immune response and inflammation-related diseases.

Ma H, Liu M, Fu R, Feng J, Ren H, Cao J Front Immunol. 2023; 14:1086192.

PMID: 36860877 PMC: 9970293. DOI: 10.3389/fimmu.2023.1086192.

Targeted protein degradation as an antiviral approach.

Chakravarty A, Yang P Antiviral Res. 2022; 210:105480.

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