Ubiquitinated gasdermin D mediates arsenic-induced pyroptosis and hepatic insulin resistance in rat liver

Zhu, Yuhan; Zhang, Jingyuan; Yao, Xiaofeng; Qiu, Tianming; Jiang, Liping; Wang, Ningning; Shi, Yan; Wu, Chenbing; Yuan, Weizhuo; Yang, Guang; Liu, Xiaofang; Bai, Jie; Men, Lili; Sun, Xiance

doi:10.1016/j.fct.2021.112771

Cited by 15 publications

(12 citation statements)

References 61 publications

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“…The stability of GSDMD was regulated by ubiquitination 40 . In PBMCs isolated from patients with mild and severe periodontitis, the ubiquitination of GSDMD was obviously decreased compared to PBMCs isolated from healthy donors (Figure 2A).…”

Section: Resultsmentioning

confidence: 98%

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Synoviolin alleviates GSDMD‐mediated periodontitis by suppressing its stability

Pang

Liu

et al. 2023

Immunity Inflam & Disease

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Introduction Inflammasome and pyroptosis play important roles in periodontitis. Gasdermin D (GSDMD), a key factor in pyroptosis, is cleaved by caspase‐1 and regulated by ubiquitination. Synoviolin is a ubiquitin E3 ligase that interacts with GSDMD. In this study, the effects of Synoviolin on inflammasome activation and periodontitis were explored. Methods The expression of IL‐1β, GSDMD, and Synoviolin in peripheral blood mononuclear cells from patients with periodontitis was determined. The interaction between GSDMD and Synoviolin was studied. The cytokine level in gingival tissues and the distance from the cementoenamel junction to the alveolar bone crest were measured in mice with Synoviolin deficiency in myeloid cells. Results We reported that elevated mRNA and protein levels of IL‐1β and GSDMD, decreased levels of Synoviolin mRNA and protein, and decreased ubiquitination of GSDMD were associated with periodontitis. Synoviolin interacted with GSDMD. Synoviolin‐deficient bone marrow‐derived macrophages had increased IL‐1β and IL‐18 secretion after ATP stimulation. Mice with Synoviolin deficiency in myeloid cells had more severe periodontitis and upregulated IL‐1β and IL‐18. Conclusions Therefore, we conclude that Synoviolin suppresses inflammasome activation and periodontitis by regulating GSDMD stability.

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Section: Resultsmentioning

confidence: 98%

“…Pyroptosis is a process of cellular self‐destruction which is involved in periodontitis. GSDMD, the key factor in pyroptosis, is regulated by ubiquitination 40,41 . Here, we evaluated the effects of the E3 ligase Synoviolin on GSDMD expression and on periodontitis.…”

Section: Discussionmentioning

confidence: 99%

Synoviolin alleviates GSDMD‐mediated periodontitis by suppressing its stability

Pang

Liu

et al. 2023

Immunity Inflam & Disease

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“…Their data showed reduced GSDMD Lys48 and Lys63 polyubiquitylation inhibiting its degradation via proteasome to promote pyroptosis. These findings could have an impact on prevention and treatment of type 2 diabetes ( Zhu et al, 2022 ).…”

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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“…Ubibrowser software was used to investigate other potential E3 ubiquitin ligases that interact with GSDMD, such as Mindbomb Homologue 2 (MIB2) and Nedd4. Another study showed that sodium arsenite (NaAsO2) prevented GSDMD degradation by inhibiting K48- and K63-linked ubiquitination, leading to GSDMD accumulation and pyroptosis 115 . Consequently, uncontrolled pyroptosis worsens liver damage and insulin resistance.…”

Section: Gasdermins' Characteristics and Cleavage Mechanismsmentioning

confidence: 99%

Precise Orchestration of Gasdermins' Pore-Forming Function by Posttranslational Modifications in Health and Disease

Jiang,

Liu,

Kang

et al. 2023

Int. J. Biol. Sci.

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Gasdermins (GSDMs) serve as pivotal executors of pyroptosis and play crucial roles in host defence, cytokine secretion, innate immunity, and cancer. However, excessive or inappropriate GSDMs activation is invariably accompanied by exaggerated inflammation and results in tissue damage. In contrast, deficient or impaired activation of GSDMs often fails to promptly eliminate pathogens, leading to the increasing severity of infections. The activity of GSDMs requires meticulous regulation. The dynamic modulation of GSDMs involves many aspects, including autoinhibitory structures, proteolytic cleavage, lipid binding and membrane translocation (oligomerization and pre-pore formation), oligomerization (pore formation) and pore removal for membrane repair. As the most comprehensive and efficient regulatory pathway, posttranslational modifications (PTMs) are widely implicated in the regulation of these aspects. In this comprehensive review, we delve into the complex mechanisms through which a variety of proteases cleave GSDMs to enhance or hinder their function. Moreover, we summarize the intricate regulatory mechanisms of PTMs that govern GSDMs-induced pyroptosis.

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Ubiquitinated gasdermin D mediates arsenic-induced pyroptosis and hepatic insulin resistance in rat liver

Cited by 15 publications

References 61 publications

Synoviolin alleviates GSDMD‐mediated periodontitis by suppressing its stability

Synoviolin alleviates GSDMD‐mediated periodontitis by suppressing its stability

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

Precise Orchestration of Gasdermins' Pore-Forming Function by Posttranslational Modifications in Health and Disease

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