| First Author | Rodriguez DA | Year | 2024 |
| Journal | Cell Rep | Volume | 43 |
| Issue | 6 | Pages | 114335 |
| PubMed ID | 38850531 | Mgi Jnum | J:360956 |
| Mgi Id | MGI:7665922 | Doi | 10.1016/j.celrep.2024.114335 |
| Citation | Rodriguez DA, et al. (2024) The interaction between RIPK1 and FADD controls perinatal lethality and inflammation. Cell Rep 43(6):114335 |
| abstractText | Perturbation of the apoptosis and necroptosis pathways critically influences embryogenesis. Receptor-associated protein kinase-1 (RIPK1) interacts with Fas-associated via death domain (FADD)-caspase-8-cellular Flice-like inhibitory protein long (cFLIP(L)) to regulate both extrinsic apoptosis and necroptosis. Here, we describe Ripk1-mutant animals (Ripk1(R588E) [RE]) in which the interaction between FADD and RIPK1 is disrupted, leading to embryonic lethality. This lethality is not prevented by further removal of the kinase activity of Ripk1 (Ripk1(R588E K45A) [REKA]). Both Ripk1(RE) and Ripk1(REKA) animals survive to adulthood upon ablation of Ripk3. While embryonic lethality of Ripk1(RE) mice is prevented by ablation of the necroptosis effector mixed lineage kinase-like (MLKL), animals succumb to inflammation after birth. In contrast, Mlkl ablation does not prevent the death of Ripk1(REKA) embryos, but animals reach adulthood when both MLKL and caspase-8 are removed. Ablation of the nucleic acid sensor Zbp1 largely prevents lethality in both Ripk1(RE) and Ripk1(REKA) embryos. Thus, the RIPK1-FADD interaction prevents Z-DNA binding protein-1 (ZBP1)-induced, RIPK3-caspase-8-mediated embryonic lethality, affected by the kinase activity of RIPK1. |
