A molecular switch from STAT2-IRF9 to ISGF3 underlies interferon-induced gene transcription

Platanitis, Ekaterini; Demiroz, Duygu; Schneller, Anja; Fischer, Katrin; Capelle, Christophe; Hartl, Markus; Gossenreiter, Thomas; Müller, Mathias; Novatchkova, Maria; Decker, Thomas

doi:10.1038/s41467-019-10970-y

Cited by 169 publications

(253 citation statements)

References 80 publications

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“…IL‐1α/β signaling leads to MAPK and NF‐κB signaling and this has broad effects to augment inflammatory cytokine production 10 . Finally, IFN signaling leads to the formation of the IFN‐stimulated gene factor 3 (ISGF3) transcription factor that drives the expression of IFN stimulated genes (ISGs) 11 . ISGs are a diverse group of genes whose expression generates a potent antiviral state in the cell itself and other surrounding cells.…”

Section: Signaling Pathways and Regulation Of Inflammationmentioning

confidence: 99%

Impact of age-, cancer-, and treatment-driven inflammation on T cell function and immunotherapy

Quinn

Kartikasari

Cooke

et al. 2020

Journal of Leukocyte Biology

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Many cancers are predominantly diagnosed in older individuals and chronic inflammation has a major impact on the overall health and immune function of older cancer patients. Chronic inflammation is a feature of aging, it can accelerate disease in many cancers and it is often exacerbated during conventional treatments for cancer. This review will provide an overview of the factors that lead to increased inflammation in older individuals and/or individuals with cancer, as well as those that result from conventional treatments for cancer, using ovarian cancer (OC) and multiple myeloma (MM) as key examples. We will also consider the impact of chronic inflammation on immune function, with a particular focus on T cells as they are key targets for novel cancer immunotherapies. Overall, this review aims to highlight specific pathways for potential interventions that may be able to mitigate the impact of chronic inflammation in older cancer patients.

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Section: Signaling Pathways and Regulation Of Inflammationmentioning

confidence: 99%

Impact of age-, cancer-, and treatment-driven inflammation on T cell function and immunotherapy

Quinn

Kartikasari

Cooke

et al. 2020

Journal of Leukocyte Biology

View full text Add to dashboard Cite

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“…cell type reference details BMDM Platanitis et al [61] IFNb, 1.5 hr, 250 IU/ml fibroblast Platanitis et al [61] IFNb, 1.5 hr, 250 IU/ml B Mostafavi et al [52] IFNa, 1.5 hr, 10,000 IU/ml HeLa Au-Yeung et al [1] IFNa, 2 hr, 1000 U/ml K562 ENCODE IFNa, 6 hr, N/A THP1 Platanitis et al [61] IFNb, 1.5 hr, 250 IU/ml…”

Section: Processing Transcription Datasetsmentioning

confidence: 99%

“…The large number of BMDM peaks may reflect the unique role of BMDM in innate response. The difference in peak counts between mouse and human cell types may be due to low sensitivity of ChIP antibody binding in human cells, particularly IRF9, as discussed in [61].…”

Section: Isre Signaturesmentioning

confidence: 99%

“…However, over the past two decades an array of non-canonical interferon pathways and regulators have been discovered [38]. In particular, IFN signaling can activate STATs other than STAT1 and STAT2, pathways other than JAK-STAT are activated by IFN stimulation or are involved in crosstalk with IFN signaling, and the STAT2:IRF9 dimer and other molecules other than ISGF3 can bind to ISREs [60,83,57,25,48,61].…”

Section: Introductionmentioning

confidence: 99%

“…They found that STAT2 binding at homeostasis was associated with differential expression under IFN stimulation, but that STAT2 binding could act as a repressor [74]. Several groups have compared the effects of ISGF3 binding and STAT2:IRF9 dimer binding to ISREs [25,7,6,61].…”

Section: Introductionmentioning

confidence: 99%

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Characterization and Prediction of ISRE Binding Patterns Across Cell Types Under Type I Interferon Stimulation

Leviyang

2020

Preprint

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Stimulation of cells by type I interferons (IFN) leads to the differential expression of 100s of genes known as interferon stimulated genes, ISGs. The collection of ISGs differentially expressed under IFN stimulation, referred to as the IFN signature, varies across cell types. Non-canonical IFN signaling has been clearly associated with variation in IFN signature across cell types, but the existence of variation in canonical signaling and its impact on IFN signatures is less clear. The canonical IFN signaling pathway involves binding of the transcription factor ISGF3 to IFN-stimulated response elements, ISREs. We examined ISRE binding patterns under IFN stimulation across six cell types using existing ChIPseq datasets available on the GEO and ENCODE databases. We find that ISRE binding is cell specific, particularly for ISREs distal to transcription start sites, potentially associated with enhancer elements, while ISRE binding in promoter regions is more conserved. Given variation of ISRE binding across cell types, we investigated associations between the cell type, homeostatic state and ISRE binding patterns. Taking a machine learning approach and using existing ATACseq and ChIPseq datasets available on GEO and ENCODE, we show that the epigenetic state of an ISRE locus at homeostasis and the DNA sequence of the ISRE locus are predictive of the ISRE’s binding under IFN stimulation in a cell type, specific manner, particularly for ISRE distal to transcription start sites.

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Activation of the cGAS‐STING‐IRF3 Axis by Type I and II Interferons Contributes to Host Defense

Tong,

Zou,

Wang

et al. 2024

Advanced Science

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Interferons (IFNs) activate JAK‐STAT pathways to induce downstream effector genes for host defense against invaded pathogens and tumors. Here both type I (β) and II (γ) IFNs are shown that can activate the transcription factor IRF3 in parallel with STAT1. IRF3‐deficiency impairs transcription of a subset of downstream effector genes induced by IFN‐β and IFN‐γ. Mechanistically, IFN‐induced activation of IRF3 is dependent on the cGAS‐STING‐TBK1 axis. Both IFN‐β and IFN‐γ cause mitochondrial DNA release into the cytosol. In addition, IFNs induce JAK1‐mediated tyrosine phosphorylation of cGAS at Y214/Y215, which is essential for its DNA binding activity and signaling. Furthermore, deficiency of cGAS, STING, or IRF3 impairs IFN‐β‐ or IFN‐γ‐mediated antiviral and antitumor activities. The findings reveal a novel IRF3 activation pathway parallel with the canonical STAT1/2 activation pathways triggered by IFNs and provide an explanation for the pleiotropic roles of the cGAS‐STING‐IRF3 axis in host defense.

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A molecular switch from STAT2-IRF9 to ISGF3 underlies interferon-induced gene transcription

Cited by 169 publications

References 80 publications

Impact of age-, cancer-, and treatment-driven inflammation on T cell function and immunotherapy

Impact of age-, cancer-, and treatment-driven inflammation on T cell function and immunotherapy

Characterization and Prediction of ISRE Binding Patterns Across Cell Types Under Type I Interferon Stimulation

Activation of the cGAS‐STING‐IRF3 Axis by Type I and II Interferons Contributes to Host Defense

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