Casper/c-FLIP is physically and functionally associated with NF-kappaB1 p105.

Zhiqin Li; Jingbo Zhang; Danying Chen; Hong-Bing Shu

doi:10.1016/j.bbrc.2003.08.104

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Casper/c-FLIP is physically and functionally associated with NF-kappaB1 p105.

Zhiqin Li·Jingbo Zhang·Danying Chen·Hong-Bing Shu

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Abstract

Casper/c-FLIP is a caspase-8-related molecule critically involved in regulation of death receptor-induced apoptosis. It has been shown that Casper can either promote or antagonize apoptosis and can activate the transcription factor NF-kappaB. The exact functions of Casper are controversial. To further understand how Casper signals, we searched Casper-interacting proteins by yeast two-hybrid screening. This effort identified NF-kappaB1 (p105), an atypical IkappaB molecule and the precursor of NF-kappaB subunit p50. Co-immunoprecipitation experiments indicated that Casper interacted with p105 in 293 cells and this interaction was mediated through the C-terminal IkappaB-like domain (IkappaBgamma). Overexpression of p105 and IkappaBgamma inhibited Casper-induced NF-kappaB activation and potentiated Casper-induced apoptosis. Furthermore, Casper and its C-terminal caspase-like domain inhibited p105 processing into p50. Our findings suggest that p105 is involved in Casper-mediated regulation of apoptosis and NF-kappaB activation.

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CASP8 and FADD-Like Apoptosis Regulating Protein Carrier Proteins Cell Line Humans Intracellular Signaling Peptides and Proteins NF-kappa B NF-kappa B p50 Subunit Protein Binding Protein Precursors Two-Hybrid System Techniques Journal Article Research Support, Non-U.S. Gov't

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Zhiqin Li, Jingbo Zhang, Danying Chen, Hong-Bing Shu. 2003-10-03. Casper/c-FLIP is physically and functionally associated with NF-kappaB1 p105.. https://doi.org/10.1016/j.bbrc.2003.08.104

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