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The c-FLIP-NH2 terminus (p22-FLIP) induces NF-kappaB activation.

ABSTRACT: c-FLIP proteins (isoforms: c-FLIP(L), c-FLIP(S), and c-FLIP(R)) play an essential role in the regulation of death receptor-induced apoptosis. Here, we demonstrate that the cytoplasmic NH2-terminal procaspase-8 cleavage product of c-FLIP (p22-FLIP) found in nonapoptotic malignant cells, primary T and B cells, and mature dendritic cells (DCs) strongly induces nuclear factor kappaB (NF-kappaB) activity by interacting with the IkappaB kinase (IKK) complex via the IKKgamma subunit. Thus, in addition to inhibiting apoptosis by binding to the death-inducing signaling complex, our data demonstrate a novel mechanism by which c-FLIP controls NF-kappaB activation and life/death decisions in lymphocytes and DCs.

SUBMITTER: Golks A

PROVIDER: S-EPMC2121210 | biostudies-literature | 2006 May

REPOSITORIES: biostudies-literature

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The c-FLIP-NH2 terminus (p22-FLIP) induces NF-kappaB activation.

Golks Alexander A Brenner Dirk D Krammer Peter H PH Lavrik Inna N IN

The Journal of experimental medicine 20060508 5

c-FLIP proteins (isoforms: c-FLIP(L), c-FLIP(S), and c-FLIP(R)) play an essential role in the regulation of death receptor-induced apoptosis. Here, we demonstrate that the cytoplasmic NH2-terminal procaspase-8 cleavage product of c-FLIP (p22-FLIP) found in nonapoptotic malignant cells, primary T and B cells, and mature dendritic cells (DCs) strongly induces nuclear factor kappaB (NF-kappaB) activity by interacting with the IkappaB kinase (IKK) complex via the IKKgamma subunit. Thus, in addition ...[more]

PMID: 16682493

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