ISG20, an actor of the innate immune response

Degols, Geneviève; Eldin, Patrick; Mechti, Nadir

doi:10.1016/j.biochi.2007.03.006

Cited by 60 publications

(63 citation statements)

References 49 publications

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“…According to several studies, this protein shows antiviral activity against RNA genomic viruses, such as vesicular stomatitis virus, influenza virus, and encephalomyocarditis virus. This activity is dependent on its exonuclease activity; therefore, IFN-stimulated gene 20 may act directly by degrading viral RNA (43). Similarly, Trex1 could be involved in the antiviral response against DNA genomic viruses.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Trex1 Induction by IFN-γ in Murine Macrophages

Serra

Forcales

Pereira-Lopes

et al. 2011

The Journal of Immunology

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3′ Repair exonuclease (Trex1) is the most abundant mammalian 3′→5′ DNA exonuclease with specificity for ssDNA. Trex1 deficiency has been linked to the development of autoimmune disease in mice and humans, causing Aicardi-Goutières syndrome in the latter. In addition, polymorphisms in Trex1 are associated with systemic lupus erythematosus. On the basis of all these observations, it has been hypothesized that Trex1 acts by digesting an endogenous DNA substrate. In this study, we report that Trex1 is regulated by IFN-γ during the activation of primary macrophages. IFN-γ upregulates Trex1 with the time course of an early gene, and this induction occurs at the transcription level. The half-life of mRNA is relatively short (half-life of 70 min). The coding sequence of Trex1 has only one exon and an intron of 260 bp in the promoter in the nontranslated mRNA. Three transcription start sites were detected, the one at −580 bp being the most important. In transient transfection experiments using the Trex1 promoter, we have found that two IFN-γ activation site boxes, as well as an adaptor protein complex 1 box, were required for the IFN-γ–dependent induction. By using EMSA assays and chromatin immune precipitation assays, we determined that STAT1 binds to the IFN-γ activation site boxes. The requirement of STAT1 for Trex1 induction was confirmed using macrophages from Stat1 knockout mice. We also establish that c-Jun protein, but not c-Fos, jun-B, or CREB, bound to the adaptor protein complex 1 box. Therefore, our results indicate that IFN-γ induces the expression of the Trex1 exonuclease through STAT1 and c-Jun.

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Section: Discussionmentioning

confidence: 99%

Characterization of Trex1 Induction by IFN-γ in Murine Macrophages

Serra

Forcales

Pereira-Lopes

et al. 2011

The Journal of Immunology

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“…RNases may play an important role in protection against various pathogens, including viruses and bacteria, in both cellular and extracellular regions (17). Like other exonucleases, ISG20 may play a role in cleaving both DNA and RNA.…”

Section: Function and Mechanismmentioning

confidence: 99%

“…In addition, assay data for some gene products, including ISG20, display differing antiviral activity in vitro versus in vivo (24). These findings suggest that caution must be used when interpreting results obtained overexpression of exogenous ISG20 is detrimental to cell survival (17) Thus, the activity of ISG20 must be tightly regulated (17). In addition, ISG20 may be a biomarker of some diseases and it represents a potential new target for drug screening.…”

Section: Function and Mechanismmentioning

confidence: 99%

“…Imaizumi et al reported that ISG20 may be involved in innate immunity against viral infection in vascular endothelial cells (9). Additionally, some evidence indicates that ISG20 plays a role in the innate immune response against various pathogens, including bacteria and parasites (17). For example, ISG20 may be a major effector of innate immune response against Listeria infection in macrophage cells or Mycobacterium tuberculosis and Toxoplasma gondii in DCs (33,34).…”

Section: Other Progressmentioning

confidence: 99%

“…Some hypotheses propose that ISG20 affects the development of viruses by degrading viral RNA, but it may also act indirectly on cellular factors required for viral replication or transcription (17). The mechanism underlying this activity remains unclear, but the 3'-5'exonuclease activity of ISG20 is believed to be the effector mechanism through which ISG20 mediates IFN-antiviral activity against viral RNAs (2).…”

Section: Isg20 and Virusesmentioning

confidence: 99%

See 2 more Smart Citations

Interferon-stimulated gene 20-kDa protein (ISG20) in infection and disease: Review and outlook

Zheng

Wang

Pan

2017

IRDR

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ISG20: an enigmatic antiviral RNase targeting multiple viruses

et al. 2022

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Interferon‐stimulated gene 20 kDa protein (ISG20) is a relatively understudied antiviral protein capable of inhibiting a broad spectrum of viruses. ISG20 exhibits strong RNase properties, and it belongs to the large family of DEDD exonucleases, present in both prokaryotes and eukaryotes. ISG20 was initially characterized as having strong RNase activity in vitro, suggesting that its inhibitory effects are mediated via direct degradation of viral RNAs. This mechanism of action has since been further elucidated and additional antiviral activities of ISG20 highlighted, including direct degradation of deaminated viral DNA and translational inhibition of viral RNA and nonself RNAs. This review focuses on the current understanding of the main molecular mechanisms of viral inhibition by ISG20 and discusses the latest developments on the features that govern specificity or resistance to its action.

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ISG20, an actor of the innate immune response

Cited by 60 publications

References 49 publications

Characterization of Trex1 Induction by IFN-γ in Murine Macrophages

Characterization of Trex1 Induction by IFN-γ in Murine Macrophages

Interferon-stimulated gene 20-kDa protein (ISG20) in infection and disease: Review and outlook

ISG20: an enigmatic antiviral RNase targeting multiple viruses

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