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nuclear cGAS suppresses homologous-recombination-mediated repair and promotes tumour growth; cGAS therefore represents a potential target for cancer prevention and therapy
STAG2 deficiency induces interferon responses via cGAS-STING pathway and restricts virus infection.
Data show that both cyclic GMP-AMP synthase (cGAS) and interferon-gamma inducible protein 16 (IFI16) are required for the activation of membrane protein STING (STING) and an innate immune response to exogenous DNA and DNA viruses.
duration of LVAD support negatively correlated with expression differences of PKG I, PDE5, and sGC in ICM, but not in DCM. Originating from the same activation level at LVAD implantation, cardiac unloading significantly alters key components of the cGMP-PKG pathway in DCM, but not in ICM patients.
cGAS and STING mediated detection of pneumococcal DNA in mouse macrophages to primarily stimulate type I interferon responses.
These results demonstrated that the DNA-induced phase transition of cGAS promotes cGAMP production and innate immune signaling.
Thus, the intracellular level of TREX1 pivotally modulates innate immune induction by HIV-1. Partial HIV-1 genomes are the TREX1 target and are sensed by cGAS.
This study demonstrated that HSV-1 tegument protein VP22 counteracts the cGAS/STING-mediated DNA-sensing antiviral innate immunity signaling pathway by inhibiting the enzymatic activity of cGAS.
study reports that the DENV NS2B protease cofactor targets the DNA sensor cyclic GMP-AMP synthase (cGAS) for lysosomal degradation to avoid the detection of mitochondrial DNA during infection.
This work identifies long DNA as the molecular entity stimulating the cGAS pathway upon cytosolic DNA challenge such as viral infections.
DNA damage leads to accumulation of damaged DNA in cytoplasmic foci that contain cGAS. In lung adenocarcinoma patients, low expression of cGAS is correlated with poor survival.
This study demonstrates that the HCMV tegument protein pp65 inhibits IFN-beta production by binding and inactivating cGAS early during infection. In addition, this inhibitory activity specifically targets cGAS, since it can be bypassed via the addition of exogenous cGAMP, even in the presence of pp65. Notably, STING proteasome-mediated degradation was observed in both the presence and absence of pp65.
TRIM56 E3 ligase-induced monoubiquitination of cGAS is important for cytosolic DNA sensing and IFNalphabeta production to induce anti-DNA viral immunity.
Results indicate that the rs311678 polymorphism in the cyclic GMP-AMP synthase (cGAS) gene confers genetic susceptibility to cervical precancerous lesions.
results suggest a nucleation-cooperativity-based mechanism for sensitive detection of mitochondrial DNA and pathogen genomes, and identify HMGB/TFAM proteins as DNA-structuring host factors; they provide an explanation for the peculiar cGAS dimer structure and suggest that cGAS preferentially binds incomplete nucleoid-like structures or bent DNA
cGAS localizes to micronuclei arising from genome instability in a mouse model of monogenic autoinflammation, after exogenous DNA damage and spontaneously in human cancer cells
Study and report of the structure and catalytic mechanism of Cyclic GMP-AMP synthase (cGAS).
Our results identify cGAS as mediator of an IFN-I response to HIV-1 infection in CD4(+) T cells and demonstrate that this response is modulated by the viral accessory proteins Vpr and Vpu. Thus, viral innate immune evasion is incomplete in the main target cells of HIV-1
miR-25/93 targets NCOA3, an epigenetic factor that maintains basal levels of cGAS expression, leading to repression of cGAS during hypoxia. This allows hypoxic tumour cells to escape immunological responses induced by damage-associated molecular pattern molecules, specifically the release of mitochondrial DNA.
IN this review, we highlight our current understanding of DNA sensing by cGAS and its involvement in human disease
Exhibits broad antiviral activity, most probably causing an early viral translation block.
chromosome 6 open reading frame 150
, cGAMP synthase
, cyclic GMP-AMP synthase
, mab-21 domain-containing protein 1
, protein MB21D1