USP5 attenuates NLRP3 inflammasome activation by promoting autophagic degradation of NLRP3

Cai, Baoshan; Zhao, Jian; Zhang, Yuling; Liu, Yaxing; Hong, Chun Pyo; Zheng, Yi; Zhang, Lei; Chen, Tian; Liu, Huiqing; Liu, Bingyu; Gao, Chengjiang

doi:10.1080/15548627.2021.1965426

Cited by 48 publications

(18 citation statements)

References 49 publications

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“…More recently, it has been demonstrated that USP5 DUB (ubiquitin specific peptidase 5) plays an important role in restraining the activation of the NLRP3 inflammasome independent of its deubiquitinating activity. Instead, USP5 recruits the E3-ligase MARCHF7/MARCH7 which promotes Lys48 poly-ubiquitin chains in NLRP3 and mediates its degradation through the autophagy-lysosomal pathway ( Cai et al, 2021 ). Another E3-ligase, SCF-FBXL2, has been described to negatively regulate NLRP3 inflammasome activation.…”

Section: Ubiquitylation Of Inflammasome Componentsmentioning

confidence: 99%

Posttranslational Regulation of Inflammasomes, Its Potential as Biomarkers and in the Identification of Novel Drugs Targets

Nanda

Vollmer²,

Pérez-Oliva

2022

Front. Cell Dev. Biol.

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In this review, we have summarized classical post-translational modifications (PTMs) such as phosphorylation, ubiquitylation, and SUMOylation of the different components of one of the most studied NLRP3, and other emerging inflammasomes. We will highlight how the discovery of these modifications have provided mechanistic insight into the biology, function, and regulation of these multiprotein complexes not only in the context of the innate immune system but also in adaptive immunity, hematopoiesis, bone marrow transplantation, as well and their role in human diseases. We have also collected available information concerning less-studied modifications such as acetylation, ADP-ribosylation, nitrosylation, prenylation, citrullination, and emphasized their relevance in the regulation of inflammasome complex formation. We have described disease-associated mutations affecting PTMs of inflammasome components. Finally, we have discussed how a deeper understanding of different PTMs can help the development of biomarkers and identification of novel drug targets to treat diseases caused by the malfunctioning of inflammasomes.

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Section: Ubiquitylation Of Inflammasome Componentsmentioning

confidence: 99%

Posttranslational Regulation of Inflammasomes, Its Potential as Biomarkers and in the Identification of Novel Drugs Targets

Nanda

Vollmer²,

Pérez-Oliva

2022

Front. Cell Dev. Biol.

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“…Dopamine D1 receptor signaling induces NLRP3 ubiquitination through E3 ubiquitin ligase MARCH7, which leads to autophagy-mediated degradation of NLRP3 ( Song et al, 2016 ). Ubiquitin-specific peptidase 5 (USP5) promotes the autophagic degradation of NLRP3 to attenuate NLRP3 inflammasome activation ( Cai et al, 2021 ). In C57BL/6J mice, galectin-9 facilitates p62-dependent autophagy, degrades NLRP3, and attenuates NLRP3 inflammasome activation in primary peritoneal macrophages ( Wang et al, 2021 ).…”

Section: Adiponectin and Osteoarthritismentioning

confidence: 99%

Role of adiponectin in osteoarthritis

Feng

Xiao

Bai

2022

Front. Cell Dev. Biol.

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Osteoarthritis (OA) is a widespread and most common joint disease which leads to social cost increasing accompany with aging population. Surgery is often the final treatment option. The major progression of OA includes cartilage degradation caused by chondrocytes metabolism imbalance. So, the molecular mechanisms of action in chondrocytes may provide insights into treatment methods for OA. Adiponectin is an adipokine with many biological functions in the cell metabolism. Numerous studies have illustrated that adiponectin has diverse biological effects, such as inhibition of cell apoptosis. It regulates various functions in different organs, including muscle, adipose tissue, brain, and bone, and regulates skeletal homeostasis. However, the relationship between adiponectin and cell death in the progression of OA needs further investigation. We elaborate the structure and function and the effect of adiponectin and state the correlation and intersection between adiponectin, autophagy, inflammation, and OA. From the perspective of oxidative stress, apoptosis, pyroptosis, and autophagy, we discuss the possible association between adiponectin, chondrocyte metabolism, and inflammatory factor efforts in OA. What’s more, we summarize the possible treatment methods, including the use of adiponectin as a drug target, and highlight the potential future mechanistic research. In this review, we summarize the molecular pathways and mechanisms of action of adiponectin in chondrocyte inflammation and death and the pathogenesis of OA. We also review the research on adiponectin as a target for treating OA. These studies provide a novel perspective to explore more effective treatment options considering the complex interrelationship between inflammation and metabolism in OA.

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“…USP5 functions as a scaffold to recruit the E3 enzyme MARCHF7/MARCH7, promoting the K48-linked ubiquitination of NLRP3 and subsequent autophagy-lysosomal degradation. Increased USP5 expression in mice reduced IL-1β and PMN infiltration in aluminum-induced peritonitis ( Cai et al, 2021 ). Data from another study have found that USP19 regulates kinase TBK1 lysosomal degradation; it did not change the ubiquitination of TBK1, and mutation with enzyme activity of USP19 still can bind with TBK1 and promote its degradation.…”

Section: Dubs Regulate the Antiviral Immune Signaling In The Autophagy-lysosomal Systemmentioning

confidence: 99%

Cellular Deubiquitylating Enzyme: A Regulatory Factor of Antiviral Innate Immunity

et al. 2021

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Deubiquitylating enzymes (DUBs) are proteases that crack the ubiquitin code from ubiquitylated substrates to reverse the fate of substrate proteins. Recently, DUBs have been found to mediate various cellular biological functions, including antiviral innate immune response mediated by pattern-recognition receptors (PRRs) and NLR Family pyrin domain containing 3 (NLRP3) inflammasomes. So far, many DUBs have been identified to exert a distinct function in fine-tuning antiviral innate immunity and are utilized by viruses for immune evasion. Here, the recent advances in the regulation of antiviral responses by DUBs are reviewed. We also discussed the DUBs-mediated interaction between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and antiviral innate immunity. The understanding of the mechanisms on antiviral innate immunity regulated by DUBs may provide therapeutic opportunities for viral infection.

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USP5 attenuates NLRP3 inflammasome activation by promoting autophagic degradation of NLRP3

Cited by 48 publications

References 49 publications

Posttranslational Regulation of Inflammasomes, Its Potential as Biomarkers and in the Identification of Novel Drugs Targets

Posttranslational Regulation of Inflammasomes, Its Potential as Biomarkers and in the Identification of Novel Drugs Targets

Role of adiponectin in osteoarthritis

Cellular Deubiquitylating Enzyme: A Regulatory Factor of Antiviral Innate Immunity

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