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Z‐nucleic acid binding protein (ZBP)1 (also known as DAI and DLM1) is a pathogen sensor activated by double‐strand character RNA to recruit receptor‐interacting protein (RIP) kinase via a RIP homotypic interaction motif. The activation of receptor‐interacting protein kinase (RIPK)3 and initiation of virus‐induced necroptosis were initially reported in a landmark publication Upton et al. (Cell Host Microbe...
The execution of shock following high dose E. coli lipopolysaccharide (LPS) or bacterial sepsis in mice required pro-apoptotic caspase-8 in addition to pro-pyroptotic caspase-11 and gasdermin D. Hematopoietic cells produced MyD88- and TRIF-dependent inflammatory cytokines sufficient to initiate shock without any contribution from caspase-8 or caspase-11. Both proteases had to be present to support...
Receptor-interacting protein kinase 3 (RIP3 or RIPK3) has emerged as a central player in necroptosis and a potential target to control inflammatory disease. Here, three selective small-molecule compounds are shown to inhibit RIP3 kinase-dependent necroptosis, although their therapeutic value is undermined by a surprising, concentration-dependent induction of apoptosis. These compounds interact with...
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