Z-nucleic acid-dependent inflammatory signaling pathway. ADAR1p150 and ZBP1 seem to recognize stress-induced Z-conformational nucleic acids. Although it is not experimentally demonstrated yet, the potential interplay between ADAR1p150 and ZBP1 is expected since both proteins are interferon-inducible and equally recog-nize Z-DNA/RNA through their Zα domains. The double-headed arrow indicates the nucleocytoplasmic shuttling of ADAR1p150 and ZBP1. While Z-nucleic acid-triggered ZBP1-dependent cell death pathway is currently actively being investigated, Z-DNA/RNA-dependent function of ADAR1p150 is still largely unknown. Some viruses such as vaccinia virus (VACV) can prevent host Z-DNA/RNA sensing by their Zα domain-bearing E3L protein. The mechanisms of signaling pathways with dashed lines are less well-established. Even though RIPK1-dependent NF-kB activation is well-known, how Z-DNA/RNA-dependent ZBP1 complex signals to RIPK1 remains elusive.
