Modulation of Stimulator of Interferon Genes (STING) Expression by Interferon-γ in Human Keratinocytes

Nishikawa, Yohei; Matsuzaki, Yasushi; Kimura, Kazuyuki; Rokunohe, Akiko; Nakano, Hajime; Sawamura, Daisuke

doi:10.1007/s10528-017-9832-7

Cited by 11 publications

(9 citation statements)

References 22 publications

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“…In keratinocytes, IFN‐γ but not IFN‐β, TGF‐β or TNFα was found to up‐regulate STING expression. Phosphorylated STAT1 dimers downstream of IFN‐γ sensing can bind and activate the STING promoter . In macrophages, on the other hand, type I IFN can induce STING expression, through STAT1/STAT2/p48 binding to a different region of the promoter .…”

Section: Basic Biology Of the Sting Pathwaymentioning

confidence: 99%

“…Phosphorylated STAT1 dimers downstream of IFN-γ sensing can bind and activate the STING promoter. 50 In macrophages, on the other hand, type I IFN can induce STING expression, through STAT1/STAT2/p48 binding to a different region of the promoter. 51 KDM5 family demethylases carry out additional regulation at the STING promoter by removing H3K4 trimethylation and limiting transcription.…”

Section: Mechanistic Insights Into Sting Function and Regulationmentioning

confidence: 99%

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STING pathway agonism as a cancer therapeutic

Flood

Higgs

et al. 2019

Immunological Reviews

243

183

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The fact that a subset of human cancers showed evidence for a spontaneous adaptive immune response as reflected by the T cell‐inflamed tumor microenvironment phenotype led to the search for candidate innate immune pathways that might be driving such endogenous responses. Preclinical studies indicated a major role for the host STING pathway, a cytosolic DNA sensing pathway, as a proximal event required for optimal type I interferon production, dendritic cell activation, and priming of CD8+ T cells against tumor‐associated antigens. STING agonists are therefore being developed as a novel cancer therapeutic, and a greater understanding of STING pathway regulation is leading to a broadened list of candidate immune regulatory targets. Early phase clinical trials of intratumoral STING agonists are already showing promise, alone and in combination with checkpoint blockade. Further advancement will derive from a deeper understanding of STING pathway biology as well as mechanisms of response vs resistance in individual cancer patients.

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Section: Basic Biology Of the Sting Pathwaymentioning

confidence: 99%

Section: Mechanistic Insights Into Sting Function and Regulationmentioning

confidence: 99%

STING pathway agonism as a cancer therapeutic

Flood

Higgs

et al. 2019

Immunological Reviews

243

183

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“…STING is a transmembrane protein found in mitochondria and endoplasmic reticulum that regulates IFN-promotor activation at the downstream of RIG-I [40]. Zhang et al studied the effect of USP18 (also known as UBP43) on STING and revealed that USP18 interacts with STING to affect IFN-promotor activity [41].…”

Section: Usp18 and Usp20mentioning

confidence: 99%

Regulatory interplay between deubiquitinating enzymes and cytokines

Woo

Baek

2019

Cytokine & Growth Factor Reviews

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A B S T R A C TDeubiquitinating enzymes (DUBs) are cysteine protease proteins that reverse the ubiquitination by removing ubiquitins from the target protein. With over 100 DUBs identified and categorized into at least 7 families, many DUBs interact with one or more cytokines, influencing cellular processes, such as antiviral responses, inflammatory responses, apoptosis, etc. While some DUBs influence cytokine pathway or production, some DUBs are cytokine-inducible. In this article, we summarize a list of DUBs, their interaction with cytokines, target proteins and mechanisms of action.

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“…We next examined the STING promoter sequence (−803 to +139) between 293 and 293T cells and found that their sequences were identical to one another and to published sequences [22,23]. Since there were no mutations between the promoter sequences, we hypothesized that SV40 large T antigen might be inhibiting STING promoter activity.…”

Section: Lack Of Sting Expression In 293t Cells Traces To a Defect Inmentioning

confidence: 99%

SV40 Large T Antigen Is Not Responsible for the Loss of STING in 293T Cells but Can Inhibit cGAS-STING Interferon Induction

Reus

Trivino-Soto

et al. 2020

Viruses

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Several DNA viruses have evolved antagonists to inhibit the cyclic GMP–AMP synthase (cGAS)-stimulator of interferon genes (STING) DNA-sensing immune pathway. This includes DNA viral oncogenes that antagonize the cGAS-STING pathway by binding STING through the LxCxE motif. The 293T human cells are widely used in biology studies as they are highly transfectable. While parental 293 cells express high levels of STING, 293T cells lack STING and are unable to induce interferon antiviral responses to cytosolic DNA. Additionally, 293T cells express the SV40 polyomavirus large T antigen (LT) which enhances the replication of transfected DNA plasmids carrying the SV40 origin of replication. Since SV40 LT also encodes the LxCxE motif, the lack of STING expression in 293T cells is commonly assumed to be due to SV40 large T antigen. We find that SV40 LT does not alter exogenously expressed and endogenous levels of STING protein. We show that STING transcription is suppressed in 293T cells but is not driven by SV40. This study also revealed that SV40 LT does indeed inhibit cGAS-STING interferon induction, but through a mechanism distinct from other DNA virus oncogenes. Collectively, these results indicate that while SV40 LT can inhibit cGAS-STING interferon induction, it does so in an unanticipated manner.

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Modulation of Stimulator of Interferon Genes (STING) Expression by Interferon-γ in Human Keratinocytes

Cited by 11 publications

References 22 publications

STING pathway agonism as a cancer therapeutic

STING pathway agonism as a cancer therapeutic

Regulatory interplay between deubiquitinating enzymes and cytokines

SV40 Large T Antigen Is Not Responsible for the Loss of STING in 293T Cells but Can Inhibit cGAS-STING Interferon Induction

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