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

Alexander Golks, Dirk Brenner, Peter H. Krammer*, Inna N. Lavrik

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

162 Citations (Scopus)

Abstract

c-FLIP proteins (isoforms: c-FLIPL, c-FLIPS, and c-FLIPR) play an essential role in the regulation of death receptor-induced apoptosis. Here, we demonstrate that the cytoplasmic NH 2-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 κB (NF-κB) activity by interacting with the IκB kinase (IKK) complex via the IKKγ 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-κB activation and life/death decisions in lymphocytes and DCs. JEM

Original languageEnglish
Pages (from-to)1295-1305
Number of pages11
JournalJournal of Experimental Medicine
Volume203
Issue number5
DOIs
Publication statusPublished - 15 May 2006
Externally publishedYes

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