Dual targeting of RIG-I and MAVS by MARCH5 mitochondria ubiquitin ligase in innate immunity

Park, Yeon-Ji; Oanh, Nguyen Thi Kim; Heo, June Seok; Kim, Seong-Gwang; Lee, Ho-Soo; Lee, Hyojoon; Lee, Jae-Ho; Kang, Ho Chul; Lim, Wonchung; Yoo, Young-Suk; Cho, Hyeseong

doi:10.1016/j.cellsig.2019.109520

Cited by 29 publications

(32 citation statements)

References 30 publications

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“…While cell biological models will be important for this, some of mechanistic insights to these regulatory mechanisms can likely be exclusively be achieved through biochemical and structural analyses. [77,78] TRIM40 [80] MARCH5 [79] CYLD [67,68] USP14 [71] USP21 [70] USP27X [73] USP3 [69] USP25 [72] MDA5…”

Section: Discussionmentioning

confidence: 99%

“…Well-studied immune proteins have often been reported to be post-translationally controlled by a multitude of regulators, which raises the question why so many enzymes would be engaged on single targets. For instance, at least six DUBs (Cylindromatosis (CYLD) [67,68], USP3 [69], USP21 [70], USP14 [71], USP25 [72], and USP27X [73]) have been proposed to counteract K63-linked ubiquitination of the RNA-sensor RIG-I, in addition to at least six E3 ligases (RNF125 [74], CBL [75], RNF122 [76], Stress Induced Phosphoprotein 1 (STIP1) Homology And U-Box Containing Protein 1 (STUB1) [77,78], Membrane Associated Ring-CH-Type Finger 5 (MARCH5) [79], and TRIM40 [80]), which reduce protein levels of RIG-I via the ubiquitin-proteasome system.…”

Section: Figurementioning

confidence: 99%

“…Mechanistically, MARCH5 was shown to induce K48-linked ubiquitination of MAVS at K7 and K500 thereby promoting its proteasomal degradation [96], although how the specific interaction with MAVS upon stimulation is achieved remains to be determined. It could be that MARCH5 has a broader ubiquitination effects in the activated RLR-MAVS complex, as a recent study showed that MARCH5 also conjugated K48-linked polyubiquitin chains to RIG-I at K193 and K203 in its CARD domain [79].…”

Section: March5mentioning

confidence: 99%

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

Budroni

Versteeg

2021

Viruses

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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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Section: Discussionmentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Section: March5mentioning

confidence: 99%

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

Budroni

Versteeg

2021

Viruses

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“…A specific ubiquitination inhibitor MG132 (Sangon Biotech Co., Ltd.) ( 23 ) 10 µM was added to cells that had been transfected with pEGFP-C1-ITCH after incubation for 44 h.…”

Section: Methodsmentioning

confidence: 99%

ITCH regulates oxidative stress induced by high glucose through thioredoxin interacting protein in cultured human lens epithelial cells

et al. 2020

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Thioredoxin (Trx) is an important protein that controls oxidative damage in almost all eukaryotic cells. Trx interaction protein (Txnip) has been reported to negatively regulate the bioavailability of Trx and inhibit its biological function. The e3 ubiquitin ligase iTcH can specifically degrade Txnip via ubiquitination. The apoptosis of human lens epithelial cells (Hlecs), which are highly sensitive to redox caused by oxidative stress, is a significant factor for the development of sugar cataract in a high-glucose environment. However, whether Trx, Txnip and iTcH contribute to the progression of sugar cataracts and the underlying mechanisms remain unknown, and thus, identifying these were the aims of the present study. The present results suggested that the expression levels of Trx, Txnip and iTcH in Hlecs cultured with different glucose concentrations were detected by reverse transcription-quantitative Pcr and western blotting, and the apoptotic rate of the cells was detected by flow cytometry and superoxide detection assay. The interaction between iTcH and Txnip was determined by co-localization immunofluorescence and co-immunoprecipitation. in addition, a vector and small interfering rna of iTcH were transfected to overexpress and knockdown iTcH, respectively, to alter the expression of downstream proteins and cell apoptosis. it was found that Txnip was highly expressed in cultured Hlecs in high-glucose environment, and the antioxidative function of Trx was restricted and suppressed, thus promoting apoptosis. The overexpression of iTcH increased the expression of Trx and decreased oxidative stress and apoptosis by decreasing Txnip in cultured Hlecs, while downregulation of iTcH significantly decreased the expression of Trx and enhanced oxidative stress and apoptosis. Therefore, the present results indicated that iTcH could regulate the apoptosis of Hlecs that were cultured in high-glucose concentration and that it may be a treatment target for sugar cataract.

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“…Regardless of how the interaction is induced, once the complex is complete, innate immune antiviral responses can ensue via activation of IRF-3 and NF-κB signaling [157,158]. MAVS can be sent off for proteasomal mediated degradation by several E3 ubiquitin ligases including the E3 ligases Ring Finger Protein 5 (RNF5) and membrane-associated ring finger (C3HC4) 5 (MARCH5) [159,160]. In the absence of iRhom2, murine innate immunity to Vesicular Stomatitis Virus (VSV) infection was considerably impaired leading to neurological symptoms in all iRhom2 deficient mice compared to 60% of wild-type mice.…”

Section: Mavs and Stingmentioning

confidence: 99%

iRhom2: An Emerging Adaptor Regulating Immunity and Disease

Al-Salihi

Lang

2020

IJMS

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The rhomboid family are evolutionary conserved intramembrane proteases. Their inactive members, iRhom in Drosophila melanogaster and iRhom1 and iRhom2 in mammals, lack the catalytic center and are hence labelled “inactive” rhomboid family members. In mammals, both iRhoms are involved in maturation and trafficking of the ubiquitous transmembrane protease a disintegrin and metalloprotease (ADAM) 17, which through cleaving many biologically active molecules has a critical role in tumor necrosis factor alpha (TNFα), epidermal growth factor receptor (EGFR), interleukin-6 (IL-6) and Notch signaling. Accordingly, with iRhom2 having a profound influence on ADAM17 activation and substrate specificity it regulates these signaling pathways. Moreover, iRhom2 has a role in the innate immune response to both RNA and DNA viruses and in regulation of keratin subtype expression in wound healing and cancer. Here we review the role of iRhom2 in immunity and disease, both dependent and independent of its regulation of ADAM17.

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Dual targeting of RIG-I and MAVS by MARCH5 mitochondria ubiquitin ligase in innate immunity

Cited by 29 publications

References 30 publications

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

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

ITCH regulates oxidative stress induced by high glucose through thioredoxin interacting protein in cultured human lens epithelial cells

iRhom2: An Emerging Adaptor Regulating Immunity and Disease

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