OTUD7B deubiquitinates SQSTM1/p62 and promotes IRF3 degradation to regulate antiviral immunity

Xie, Weidong; Tian, Shuo; Yang, Jiahui; Cai, Sihui; Zhou, Tao; Wu, Yiming; Chen, Zhiyun; Ji, Yanqin; Cui, Jun

doi:10.1080/15548627.2022.2026098

Cited by 33 publications

(16 citation statements)

References 44 publications

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“…Furthermore, p62 functions as a cargo receptor for the degradation of proteins in the inflammation pathway. During viral infection or dsDNA stimulation, p62-mediated autophagy facilitates the degradation of cGAS, STING, and IRF3, which are key components of the cGAS-STING pathway (30,(40)(41)(42). Consequently, p62 exerts negative control over the cGAS-STING pathway, thereby regulating type I IFN signaling during virus infection (30,41,42).…”

Section: Discussionmentioning

confidence: 99%

Histone chaperone HIRA, Promyelocytic Leukemia (PML) protein and p62/SQSTM1 coordinate to regulate inflammation during cell senescence

Dasgupta

Xue

Arnold

et al. 2023

Preprint

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Cellular senescence, a stable proliferation arrest caused by a range of cellular stresses, is a bona fide cause of cell and tissue aging. As well as proliferation arrest, cell senescence is associated with a potent pro-inflammatory phenotype, the senescence-associated secretory phenotype (SASP). Recent studies have shown the importance of cytoplasmic DNA and chromatin, either reverse transcribed expressed retrotransposons or cytoplasmic chromatin fragments (CCF) expelled from the nucleus, in activation of nuclear SASP gene expression via the cGAS/STING cytoplasmic DNA-sensing pathway. As a source of chronic inflammation, over the long term SASP promotes tissue aging and disease. Thus, it is important to better define the mechanism of SASP activation in senescence. We show here that both the Promyelocytic Leukemia (PML) protein and HIRA histone chaperone are required for SASP expression in senescent cells. PML protein is the key organizer of PML nuclear bodies, nuclear features up to 1 micron in diameter, containing many proteins and previously implicated in diverse cellular processes, including control of cell senescence and cellular intrinsic anti-viral immunity. HIRA is a histone chaperone best known for its ability to incorporate histone variant H3.3 into nuclear chromatin in a DNA replication-independent manner, including in non-proliferating senescent cells. HIRA localizes to PML nuclear bodies in senescent cells. We show that both HIRA and PML are required for activation of NF-kB and SASP. We found that HIRA regulates cytoplasmic NF-kB signaling in senescent cells through the CCF-cGAS-STING-TBK1 pathway. HIRA physically interacts with the autophagy cargo receptor p62 Sequestosome-1 (p62), and HIRA and p62 antagonistically regulate SASP. PML is required to maintain integrity of colocalized HIRA and p62 foci in the cell nucleus. Overall, our findings point to functions for HIRA and PML in coordination of cytoplasmic signalling and nuclear gene expression to regulate inflammation during cell senescence and aging.

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Section: Discussionmentioning

confidence: 99%

Histone chaperone HIRA, Promyelocytic Leukemia (PML) protein and p62/SQSTM1 coordinate to regulate inflammation during cell senescence

Dasgupta

Xue

Arnold

et al. 2023

Preprint

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“…As mentioned in the Mitophagy part, the virus controls the RIG-I/MAVS-mediated production of IFN-I and activation of inflammasomes by promoting mitochondrial autophagy, which will not be reiterated. OTUD7B/Cezanne (OTU deubiquitinase 7B) acts as a negative regulator of antiviral immunity by deubiquitinates SQSTM1/p62 and promotes IRF3 degradation [ 232 ]. In addition, a newly discovered selective autophagy receptor CCDC50 targets RIG-I/MDA5 and degrades them after infection with VSV, SEV, and EMCV, thereby inhibiting IRF3/7 activation and NF-κB-mediated inflammation to enhance virus replication [ 41 ] (Fig.…”

Section: Autophagy and The Innate Immunity In Viral Infectionsmentioning

confidence: 99%

The role of autophagy in viral infections

Chen

Ding

et al. 2023

J Biomed Sci

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Autophagy is an evolutionarily conserved catabolic cellular process that exerts antiviral functions during a viral invasion. However, co-evolution and co-adaptation between viruses and autophagy have armed viruses with multiple strategies to subvert the autophagic machinery and counteract cellular antiviral responses. Specifically, the host cell quickly initiates the autophagy to degrade virus particles or virus components upon a viral infection, while cooperating with anti-viral interferon response to inhibit the virus replication. Degraded virus-derived antigens can be presented to T lymphocytes to orchestrate the adaptive immune response. Nevertheless, some viruses have evolved the ability to inhibit autophagy in order to evade degradation and immune responses. Others induce autophagy, but then hijack autophagosomes as a replication site, or hijack the secretion autophagy pathway to promote maturation and egress of virus particles, thereby increasing replication and transmission efficiency. Interestingly, different viruses have unique strategies to counteract different types of selective autophagy, such as exploiting autophagy to regulate organelle degradation, metabolic processes, and immune responses. In short, this review focuses on the interaction between autophagy and viruses, explaining how autophagy serves multiple roles in viral infection, with either proviral or antiviral functions.

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“…PRKN (Parkin) could negatively regulate the antiviral response by degradation of TRAF3 [29,49,50]. OTUD7B serves as a deubiquitinase of P62/SQSTM1 and enhances the degradation of IRF-3 [51,52]. SIRT2 dysregulates autophagy in highfat-exposed immune-tolerant macrophages, and the knockdown of SIRT2 increases basal autophagy [53][54][55].…”

Section: Discussionmentioning

confidence: 99%

Transcriptome Analysis of Retinoic Acid-Inducible Gene I Overexpression Reveals the Potential Genes for Autophagy-Related Negative Regulation

Tan

Yang

et al. 2022

Cells

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Retinoic acid-inducible gene I (RIG-I) serves as an essential viral RNA sensor for innate immune. The activation of the RIG-I-like receptors (RLRs) pathway triggers many regulations for the outcome of type I interferon, including ubiquitination, dephosphorylation, ISGylation, and autophagy. However, the autophagy-related regulation of RIG-I is still not fully understood. To investigate the potentially unknown genes related to autophagy-related regulation of RIG-I, we firstly confirm the induction of autophagy derived by overexpression of RIG-I. Furthermore, the autophagy inducer and inhibitor drugs were used in different assays. The results showed autophagy could control the activation of RLRs pathway and expression of exogenous RIG-I. In addition, we carried out the transcriptome analysis of overexpression of RIG-I in vitro. Differentially expressed genes (DEGs) in GO and KEGG signaling pathways enrichment provided a newly complex network. Finally, the validation of qPCR indicated that the DEGs PTPN22, PRKN, OTUD7B, and SIRT2 were correlated to the negative regulation of excessive expression of RIG-I. Taken together, our study contributed new insights into a more comprehensive understanding of the regulation of excessive expression of RIG-I. It provided the potential candidate genes for autophagy-related negative regulation for further investigation.

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OTUD7B deubiquitinates SQSTM1/p62 and promotes IRF3 degradation to regulate antiviral immunity

Cited by 33 publications

References 44 publications

Histone chaperone HIRA, Promyelocytic Leukemia (PML) protein and p62/SQSTM1 coordinate to regulate inflammation during cell senescence

Histone chaperone HIRA, Promyelocytic Leukemia (PML) protein and p62/SQSTM1 coordinate to regulate inflammation during cell senescence

The role of autophagy in viral infections

Transcriptome Analysis of Retinoic Acid-Inducible Gene I Overexpression Reveals the Potential Genes for Autophagy-Related Negative Regulation

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