Mus musculus strain:129/SVJAe
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA694789 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Atrx deletion impairs cGAS-STING signaling and increases response to radiation and oncolytic herpesvirus in soft tissue sarcoma
| PRJNA698482 | ENA
Project description:RNA sequencing of isogenic ATRX wild-type (WT) and ATRX knockout (KO) paired isogenic cell lines treated with either 1.)interferon stimulatory DNA (ISD) and harvested 24 hours after treatment, 2)4 Gy ionizing radiation and harvested 36 hours after treatment, or 3) untreated control. These experiments help determine the differential impact of ATRX mutational status on cGAS-STING and type-I interferon signaling in soft tissue sarcoma.
2021-02-02 | GSE165878 | GEO
Project description:RNA sequencing of a primary tumors from a sarcoma genetically engineerted mouse model with activation of oncogenic Kras, deletion of p53 and deletion of Atrx, as compared to control sarcomas with identical genetic alterations but with wild-type Atrx. Tumors were either untreated or recieved 20 Gy of ionizing radiation and were harvested at 4 hrs, 3 day, or 6 day timepoints post treatment. For cell lines, isogenic ATRX wild-type (WT) and ATRX knockout (KO) paired isogenic cell lines treated with either 1.)interferon stimulatory DNA (ISD) and harvested 24 hours after treatment, 2)4 Gy ionizing radiation and harvested 36 hours after treatment, or 3) untreated control. These experiments help determine the differential impact of ATRX mutational status on cGAS-STING and type-I interferon signaling in soft tissue sarcoma.
2021-03-06 | GSE167537 | GEO
Project description:The DNA exonuclease TREX1 degrades endogenous cytosolic DNA. Cytosolic DNA triggers the cGAS/STING pathway which increases type I interferon. To investigate the physiological significance of TREX1 loss on in vivo tumor growth, we implanted control and TREX1-deficient CT26 tumor cells into immunocompetent BALB/c hosts.Tumor cells were collected 7 days after tumors reached around 200mm3.
2024-03-12 | E-MTAB-13816 | biostudies-arrayexpress
Project description:Gammaherpesviruses, including Kaposi’s sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV), are DNA viruses that are globally associated with human cancers and establish lifelong latency in the human population. Detection of gammaherpesviral infection by the cGAS-STING innate immune DNA-sensing pathway is critical for suppressing viral reactivation from latency, a process that promotes viral pathogenesis and transmission. We report that Barrier-to-autointegration factor 1 (BAF)-mediated suppression of the cGAS-STING signaling pathway is necessary for reactivation of KSHV and EBV. We demonstrate a novel role for BAF in destabilizing cGAS expression and show that BAF expression in latently infected, reactivating, or uninfected cells leads to suppression of type I interferon-mediated antiviral responses and inhibition of viral replication. Furthermore, BAF overexpression resulted in decreased cGAS expression at the protein level. These results establish BAF as a key regulator of the lifecycle of gammaherpesviruses and a potential target for treating viral infections and malignancies.
2022-12-12 | GSE200781 | GEO
Project description:Type I interferon (IFN) signalling is tightly controlled. Upon recognition of DNA by cyclic GMP-AMP synthase (cGAS), stimulator of interferon genes (STING) translocates along the endoplasmic reticulum (ER)-Golgi axis to induce IFN signalling. Afterwards, signal termination is achieved through autophagic degradation of STING, or STING recycling by retrograde COPI-mediated transport. Here we identify the GTPase ARF1 as a negative regulator of cGAS-STING signaling. Heterozygous ARF1 missense mutations cause a novel type I interferonopathy associated with enhanced IFN stimulated gene production. Expression of patient-derived, GTPase-defective, ARF1 in cell lines and primary cells results in increased cGAS-STING dependent type I IFN signalling. Mechanistically, mutated ARF1 both induces activation of cGAS by aberrant mitochondrial DNA, and promotes accumulation of active STING at the Golgi/ERGIC due to defective COPI retrograde transport. Our data establish ARF1 as a key factor in cGAS-STING homeostasis, which is required to maintain mitochondrial integrity and promote STING recycling.
2022-06-23 | MSV000089711 | MassIVE
Project description:Microbial infection, the strong trigger to directly induce inflammation in brain, is long considered a risk factor of Alzheimer’s disease, but how these infections contribute to neurodegeneration remains underexplored. Using a modified herpesvirus potentially relevant to this disease, we found that its infection promotes tau-related pathology in part via activating neuroimmune cGAS-STING pathway in the tau mouse models. These represent a causal link of environmental infectious factors and neurodegenerative diseases.
2024-04-11 | GSE229411 | GEO
Project description:Histone deacetylase 6 (HDAC6), a member of the class IIB HDAC family, has distinct biological functions through primarily deacetylating cytoplasmic non-histone proteins. However, its regulatory role in response to DNA virus infection remains elusive. Herein, we find that HDAC6 is a negative regulator of the cGAS-STING signaling pathway. HDAC6 deacetylase activity is increased in the early stage of Herpes simplex virus 1 (HSV-1) infection, and HDAC6 deficiency or inhibition of its deacetylase activity markedly promotes the activation of the cGAS-STING axis, resulting in increased expression of type I interferon (IFN) and a decrease in HSV-1 infection. Consistently, the Hdac6-/- mice exhibit increased resistance to HSV-1 infection and HSV-1 induced encephalitis (HSE). The HDAC6-interactome and Acetylome proteomics assays reveal that HDAC6 interacts with and deacetylates Tripartite motif protein 56 (TRIM56) at K110 within the B-box1 domain, leading to the reduced monoubiquitination and DNA binding of cGAS by TRIM56. In addition, acetylation of TRIM56 K110 is key to its binding to HDAC6 and regulating the IFN response, as evidenced by the opposing outcomes observed upon overexpressing TRIM56 K110Q and K110R on the cGAS-STING axis. Overexpression of TRIM56 K110Q further enhances protection against HSV-1 infection and HSE pathogenesis in mice, alongside increased activation of the cGAS-STING-IFN axis. Interestingly, TRIM56 displays species-specific K110, which differentially regulates the IFN response in humans and mice. Furthermore, HDAC6 accumulates in the cytoplasm and is phosphorylated by the viral protein US3, which increases its deacetylase activity and interaction with TRIM56 in the early infection stage. Together, our findings disclose that HDAC6 negatively regulates cGAS activation through TRIM56 deacetylation, suggesting a potential antiviral strategy by inhibiting HDAC6 activity.
2024-12-21 | PXD046808 | Pride
Project description:The cGAS-STING signalling has been well recognized as the major pathway response to self and non-self DNA molecule in cytoplasm. Here, we measured the temporal transcriptome dynamic changes after cGAS-STING signalling activation based on cGAS specific agonist G3-YSD transfection
2022-12-09 | GSE207458 | GEO
Project description:Mounting evidence demonstrates that cGAS-STING signaling is the major pathway in sensing cytosolic DNAs. However, aberrant accumulation of self DNA molecules in Trex1 (a 3'-to-5' DNA exonuclease) deficient cells usually causes over-activation of cGAS-STING signaling, which is associated with the pathology of several autoimmune diseases. Here, we investigated gene expression changes in BMDM cells of Trex1 knockout mice after manipulating cGAS-STING signaling activity via treatment of two STING antagonists (SN-011 and H151) .
2021-05-26 | GSE143830 | GEO