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The Cyclopeptide Astin C Specifically Inhibits the Innate Immune CDN Sensor STING.

Cell reports | 2018

cGAS-STING signaling is essential for innate immunity. Its misregulation promotes cancer or autoimmune and autoinflammatory diseases, and it is imperative to identify effective lead compounds that specifically downregulate the pathway. We report here that astin C, a cyclopeptide isolated from the medicinal plant Aster tataricus, inhibits cGAS-STING signaling and the innate inflammatory responses triggered by cytosolic DNAs. Moreover, mice treated with astin C are more susceptible to HSV-1 infection. Consistently, astin C markedly attenuates the autoinflammatory responses in Trex1-/- BMDM cells and in Trex1-/- mouse autoimmune disease model. Mechanistically, astin C specifically blocks the recruitment of IRF3 onto the STING signalosome. Collectively, this study characterizes a STING-specific small-molecular inhibitor that may be applied for potentially manipulating the STING-mediated clinical diseases.

Pubmed ID: 30566866 RIS Download

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GenBank (tool)

RRID:SCR_002760

NIH genetic sequence database that provides annotated collection of all publicly available DNA sequences for almost 280 000 formally described species (Jan 2014) .These sequences are obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects, including whole-genome shotgun (WGS) and environmental sampling projects. Most submissions are made using web-based BankIt or standalone Sequin programs, and GenBank staff assigns accession numbers upon data receipt. It is part of International Nucleotide Sequence Database Collaboration and daily data exchange with European Nucleotide Archive (ENA) and DNA Data Bank of Japan (DDBJ) ensures worldwide coverage. GenBank is accessible through NCBI Entrez retrieval system, which integrates data from major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of GenBank database are available by FTP.

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Mouse Anti-rabbit IgG (Conformation Specific) (L27A9) mAb (HRP Conjugate) (antibody)

RRID:AB_10892860

This monoclonal secondary targets IgG (Conformation Specific)

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HSV1 antibody (antibody)

RRID:AB_307320

This polyclonal targets HSV1 antibody

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c-Myc Antibody (9E10) (antibody)

RRID:AB_627268

This monoclonal targets c-Myc

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His-probe (H-3) (antibody)

RRID:AB_627727

This monoclonal targets His-probe (H-3)

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HA-Tag Antibody (F-7) (antibody)

RRID:AB_627809

This monoclonal targets HA-Tag

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Anti-Ubiquitin Antibody (P4D1) (antibody)

RRID:AB_628423

This monoclonal targets Ubiquitin

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Cleaved Caspase-3 (Asp175) Antibody (antibody)

RRID:AB_2341188

This polyclonal targets Cleaved Caspase-3 (Asp175)

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PARP Antibody (antibody)

RRID:AB_2160739

This polyclonal targets PARP

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SCAP (C-20) (antibody)

RRID:AB_656053

This polyclonal targets SCAP

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IRF-3 (D83B9) Rabbit mAb (antibody)

RRID:AB_1904036

This monoclonal targets IRF-3

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NAK antibody [EP611Y] (antibody)

RRID:AB_776632

This monoclonal targets NAK

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Phospho-STING (Ser366) (antibody)

RRID:AB_2737062

This monoclonal targets Phospho-STING (Ser366)

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STING (D2P2F) (antibody)

RRID:AB_2732796

This monoclonal targets STING

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cGAS (D1D3G) Rabbit mAb (antibody)

RRID:AB_2732795

This monoclonal targets cGAS

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HA-Tag Antibody (F-7) (antibody)

RRID:AB_627809

This monoclonal targets HA-Tag

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Anti-Ubiquitin Antibody (P4D1) (antibody)

RRID:AB_628423

This monoclonal targets Ubiquitin

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His-probe (H-3) (antibody)

RRID:AB_627727

This monoclonal targets His-probe (H-3)

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PARP Antibody (antibody)

RRID:AB_2160739

This polyclonal targets PARP

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IRF-3 (D83B9) Rabbit mAb (antibody)

RRID:AB_1904036

This monoclonal targets IRF-3

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SCAP (C-20) (antibody)

RRID:AB_656053

This polyclonal targets SCAP

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Cleaved Caspase-3 (Asp175) Antibody (antibody)

RRID:AB_2341188

This polyclonal targets Cleaved Caspase-3 (Asp175)

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NAK antibody [EP611Y] (antibody)

RRID:AB_776632

This monoclonal targets NAK

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cGAS (D1D3G) Rabbit mAb (antibody)

RRID:AB_2732795

This monoclonal targets cGAS

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STING (D2P2F) (antibody)

RRID:AB_2732796

This monoclonal targets STING

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Mouse Anti-rabbit IgG (Conformation Specific) (L27A9) mAb (HRP Conjugate) (antibody)

RRID:AB_10892860

This monoclonal secondary targets IgG (Conformation Specific)

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c-Myc Antibody (9E10) (antibody)

RRID:AB_627268

This monoclonal targets c-Myc

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HSV1 antibody (antibody)

RRID:AB_307320

This polyclonal targets HSV1 antibody

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