Format

Send to

Choose Destination
Nature. 2011 Mar 17;471(7338):363-7. doi: 10.1038/nature09852. Epub 2011 Mar 2.

Catalytic activity of the caspase-8-FLIP(L) complex inhibits RIPK3-dependent necrosis.

Author information

1
Dept. of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.

Abstract

Caspase-8 has two opposing biological functions--it promotes cell death by triggering the extrinsic pathway of apoptosis, but also has a survival activity, as it is required for embryonic development, T-lymphocyte activation, and resistance to necrosis induced by tumour necrosis factor-α (TNF-α) and related family ligands. Here we show that development of caspase-8-deficient mice is completely rescued by ablation of receptor interacting protein kinase-3 (RIPK3). Adult animals lacking both caspase-8 and RIPK3 display a progressive lymphoaccumulative disease resembling that seen with defects in CD95 or CD95-ligand (also known as FAS and FASLG, respectively), and resist the lethal effects of CD95 ligation in vivo. We have found that caspase-8 prevents RIPK3-dependent necrosis without inducing apoptosis by functioning in a proteolytically active complex with FLICE-like inhibitory protein long (FLIP(L), also known as CFLAR), and this complex is required for the protective function.

PMID:
21368763
PMCID:
PMC3077893
DOI:
10.1038/nature09852
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center