RIP1 kinase activity-dependent roles in embryonic development of Fadd-deficient mice.

ABSTRACT: RIP1 is an essential regulator of TNF-induced signaling complexes mediating NF-κB activation, apoptosis and necroptosis. Loss of Rip1 rescues the embryonic lethality of Fadd or Caspase-8-deficient mice, even though the double knockout mice die shortly after birth like Rip1-deficient mice. Recent studies demonstrated that mice expressing RIP1 kinase-dead mutants developed normally and resisted necroptotic stimuli in vitro and in vivo. However, the impact of RIP1 kinase activity on Fadd^-/- embryonic development remains unknown. Here, we engineered two RIP1 kinase inactive mutant mouse lines, a Rip1^K45A/K45A mouse line as previously reported and a novel Rip1^Δ/Δ mouse line with an altered P-loop in the kinase domain. While RIP1^K45A could not rescue t

SUBMITTER: Liu Y 

PROVIDER: S-EPMC5520462 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature