Fig. 4
The role of BRD4 in regulating the STING1 pathway in antiviral immunity. Cytoplasmic DNA derived from various viruses activates CGAS and produces endogenous cyclic dinucleotide cGAMP, which binds to STING1 located in the endoplasmic reticulum, and then promotes the dimerization and translocation of STING1 from the ER to the perinuclear region. During trafficking, STING1 recruits and activates TBK1, stimulates the phosphorylation and nuclear translocation of IRF3, and to a lesser extent NFKB1, which leads to the production of type 1 IFN and other inflammatory cytokines (e.g., IL). The nuclear activity of IRF3 and NFKB1 is inhibited by BRD4. In addition, after BRD4 inhibition, the activation of DDR can induce the release of host dsDNA from the nucleus to the cytoplasm, leading to further activation of the CGAS-STING1 pathway to limit viral infection. Abbreviations: BRD4, bromodomain containing 4; cGAMP, cyclic GMP-AMP; CGAS, cyclic GMP-AMP synthase; DDR, DNA damage response; dsDNA, double-stranded DNA; IFN, interferon; IL, interleukin; IRF3, interferon regulatory factor 3; NFKB1, nuclear factor kappa B subunit 1; STING1, stimulator of interferon response cGAMP interactor 1; TBK1, TANK binding kinase 1
