FLIP_L permits apoptotic and inflammatory signaling and inhibits necroptosis in mice without Caspase-8 oligomerization.

ABSTRACT: Caspase-8 signaling has proapoptotic, antinecroptotic, and proinflammatory signaling roles dependent on interaction with the adapter molecule FADD, oligomerization, and autocleavage. Previously, a Caspase-8 binding partner cFLIP_L (FLIP, encoded by Cflar) was shown to prevent Caspase-8-dependent apoptosis, but permit Caspase-8-dependent inhibition of necroptosis. We sought to explore the role of FLIP in Caspase-8-dependent apoptosis induction, necroptosis inhibition, and inflammatory signaling inhibition in vitro and in vivo. We provide evidence that in mice with a mutation that prevents Caspase-8 oligomerization (Casp8^FGLG/FGLG), FLIP is necessary to inhibit necroptosis, promote apoptosis, regulate inflammation, and control lymphoproliferative disease. U

SUBMITTER: Shaw JJP 

PROVIDER: S-EPMC12012507 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature