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GSE51199
Mus musculus
6 Downloadable Samples
Illumina MouseWG-6 v2.0 expression beadchip
Description
Activation of the STING (Stimulator of Interferon Genes) pathway by microbial or self-DNA, as well as cyclic di nucleotides (CDN), results in the induction of numerous genes that suppress pathogen replication and facilitate adaptive immunity. However, sustained gene transcription is rigidly prevented to avoid lethal STING-dependent pro-inflammatory disease by mechanisms that remain unknown. We demonstrate here that after autophagy-dependent STING delivery of TBK1 (TANK-binding kinase 1) to endosomal/lysosomal compartments and activation of transcription factors IRF3 (interferon regulatory factors 3) and NF-B (nuclear factor kappa beta), that STING is subsequently phosphorylated by serine/threonine UNC-51-like kinase (ULK1/ATG1) and IRF3 function is suppressed. ULK1 activation occurred following disassociation from its repressor adenine monophosphate activated protein kinase (AMPK), and was elicited by CDNS generated by the cGAMP synthase, cGAS. Thus, while CDNs may initially facilitate STING function, they subsequently trigger negative-feedback control of STING activity, thus preventing the persistent transcription of innate immune genes.
Publication Title
Cyclic dinucleotides trigger ULK1 (ATG1) phosphorylation of STING to prevent sustained innate immune signaling.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Inflammation-driven carcinogenesis is mediated through STING.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 5 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Chronic stimulation of innate immune pathways by microbial agents or damaged tissue is known to promote inflammation-driven tumorigenesis by unclarified mechanisms1-3. Here we demonstrate that mutagenic 7,12-dimethylbenz(a)anthracene (DMBA), etoposide or cisplatin induces nuclear DNA leakage into the cytosol to intrinsically activate STING (Stimulator of Interferon Genes) dependent cytokine production. Inflammatory cytokine levels were subsequently augmented in a STING-dependent extrinsic manner by infiltrating phagocytes purging dying cells. Consequently, STING-/- mice, or wild type mice adoptively transferred with STING-/- bone marrow, were almost completely resistant to DMBA-induced skin carcinogenesis compared to their wild type counterparts. Our data emphasizes, for the first time, a role for STING in the induction of cancer, sheds significant insight into the causes of inflammation-driven carcinogenesis, and may provide therapeutic strategies to help prevent malignant disease
Publication Title
Inflammation-driven carcinogenesis is mediated through STING.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 1 Downloadable Sample
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Chronic stimulation of innate immune pathways by microbial agents or damaged tissue is known to promote inflammation-driven tumorigenesis by unclarified mechanisms1-3. Here we demonstrate that mutagenic 7,12-dimethylbenz(a)anthracene (DMBA), etoposide or cisplatin induces nuclear DNA leakage into the cytosol to intrinsically activate STING (Stimulator of Interferon Genes) dependent cytokine production. Inflammatory cytokine levels were subsequently augmented in a STING-dependent extrinsic manner by infiltrating phagocytes purging dying cells. Consequently, STING-/- mice, or wild type mice adoptively transferred with STING-/- bone marrow, were almost completely resistant to DMBA-induced skin carcinogenesis compared to their wild type counterparts. Our data emphasizes, for the first time, a role for STING in the induction of cancer, sheds significant insight into the causes of inflammation-driven carcinogenesis, and may provide therapeutic strategies to help prevent malignant disease
Publication Title
Inflammation-driven carcinogenesis is mediated through STING.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Homo sapiens
- 32 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip, Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
STING recognition of cytoplasmic DNA instigates cellular defense.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 20 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Gene expression analysis of wild type, STING knock-out and STAT1 knock-out Mouse Embryonic Fibroblasts (MEFs) stimulated with 90-mer dsDNA or 90-mer ssDNA. Genes whose expression that are affected by cytosolic DNA in a STING dependent manner will be identified and signaling pathways regulated by STING will be elucidated.
Publication Title
STING recognition of cytoplasmic DNA instigates cellular defense.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Gene expression analysis of dsDNA90 stimulated human telomerase fibroblasts (hTERT-BJ1) after STING siRNA treatment. Genes whose expression that are affected by cytosolic DNA in a STING dependent manner will be identified and signaling pathways regulated by STING will be elucidated.
Publication Title
STING recognition of cytoplasmic DNA instigates cellular defense.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Gene expression analysis of wild type and STING knock-out Mouse Embryonic Fibroblasts (MEFs) infected with 34.5 deleted HSV1. Genes whose expression that are affected by HSV1 in a STING dependent manner will be identified and signaling pathways regulated by STING will be elucidated.
Publication Title
STING recognition of cytoplasmic DNA instigates cellular defense.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 9 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Rcho-1 trophoblast stem cells can be maintained in a trophoblast stem cell state or induced to differentiate into trophoblast giant cells. During the differentiation process the PI3K pathway is constitutively activated.
Publication Title
Phosphatidylinositol 3 kinase modulation of trophoblast cell differentiation.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
DPRP (PRL8a2) is critically involved in adaptations of the placentation site to physiological stressors. DPRP (PRL8a2) restrains the expression of genes associated with ER stress.
Publication Title
Identification of target genes for a prolactin family paralog in mouse decidua.
Sample Metadata Fields
Specimen part
View Samples