Figure 1.

Trim21 negatively regulates the DDX41-mediated signaling pathway. In the early phase, DNA from diverse microbes is sensed by DDX41 in the cytosol of infected cells as a danger signal. STING recruits TBK1 to its C-terminal tail, and TBK1 then interacts with and phosphorylates IRF3/7. Phosphorylated IRF3/7 dimerizes and translocates to the nucleus, thereby promoting the expression of immune and inflammatory genes. In the late phase, Trim21 interacts with DDX41 and causes the K48-linked ubiquitination of DDX41. After ubiquitination, DDX41 is degraded by the proteasome, thus preventing ‘downstream' cytokine induction.