2024年6月14日,浙江大学医学院附属第一医院骨髓移植中心蔡真教授团队、浙江大学医学院附属邵逸夫医院/转化医学研究院谢安勇教授团队在《British Journal of Cancer》杂志在线发表论文Disruption of DNA-PKcs-mediated cGAS retention on damaged ch...
The cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) (cGAMP) synthase (cGAS) and the ER-localized stimulator of interferon genes (STING) are critical components of innate immune signaling. Though the intracellular signaling pathway was first characterized as a critical host defense ...
WT cells were able to activate IRF3 in response to htDNA or RNA (poly(I:C)) stimulation but this activation was specifically lost in cGAS−/− cells in response to DNA stimulation, indicating that cGAS is required for DNA-driven IRF3 activation in human fibroblasts (Figure 1A). As ...
DNA-PKcs phos- phorylates cGAS, inhibiting its enzymatic activity and reducing IFNB1 and CXCL-10 expression in THP-1 monocytic cells, rendering them more susceptible to viral infection84. Additionally, DNA-PKcs in bone marrow- derived macrophages activate AKT (AKR thymoma), promoting its nuclear...
IFI16 and cGAS cooperate in the activation of STING during DNA sensing in human keratinocytes Many human cells can sense the presence of exogenous DNA during infection though the cytosolic DNA receptor cyclic GMP-AMP synthase (cGAS), which produces the second messenger cyclic GMP-AMP (cGAMP). ...
However, as cGAS is primarily sequestered by chromatin in the nucleus, it remains unclear how cGAS is released from chromatin and translocated into the cytoplasm upon DNA damage, leading to cGAS-STING activation.Methods We examined the role of DNA-PKcs inhibition on cGAS-STING-mediated MM ...
Interestingly, in cGAS knockout cells, synthesis of interferon 尾1 and interferon-stimulated gene was increased upon mtDSB induction. We found that mtDSBs activated DNA-PKcs and HSPA8 in a VDAC1-dependent manner. Importantly, the mitochondrial E3 ligase MARCH5 bound ...