The interaction between RIPK1 and FADD controls perinatal lethality and inflammation.

ABSTRACT: 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

SUBMITTER: Rodriguez DA 

PROVIDER: S-EPMC11256114 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature