title: 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.
authors: Division of Immunogenetics, Tumorimmunology Program, German Cancer Research Center, D-69120 Heidelberg, Germany.
authors: Alexander
authors: A
authors: Golks
authors: Dirk
authors: D
authors: Brenner
authors: Peter H
authors: PH
authors: Krammer
authors: Inna N
authors: IN
authors: Lavrik