Dual roles of FLIP in controlling caspase-8 and their implications on cell death and survival

다국어 초록 (Multilingual Abstract)

Cellular FLIP (cFLIP; cellular FLICE inhibitory protein) is a key regulator of caspase-8 activity, and its viral homolog (vFLIP)is found in various viruses. cFLIP inhibits the caspase-8 activation in death-inducing signaling complex (DISC) when itsexpression level is high as in cancer cells. In contrast, cFLIP can also activate the caspase-8 in its lower expression leveland in lymphocyte in particular which results in the activation of NF-κB transcription factor. Recent biochemical studies onDISC has proposed that DED proteins in DISC, that are FADD, procaspase-8 & cFLIP, utilize two hydrophobic faces of theirDEDs for establishing DED-DED network for DISC assembly. Regarding the NF-κB activation, the crystal structure of K13-vFLIP showed that two grooves in the N-terminal DED in FLIP are the sites where dimeric IKKγ binds. FLIP is associatedwith various cancers seemingly through the dual functions of inhibiting apoptosis and promoting proliferation, so it wouldan attractive anti-cancer therapeutic target at either mRNA or protein level.

참고문헌 (Reference)

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