Casper/c-FLIP is physically and functionally associated with NF-kappaB1 p105.
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Li Z, Zhang J, Chen D, Shu HB
Casper/c-FLIP is physically and functionally associated with NF-kappaB1 p105.
Biochem Biophys Res Commun. 2003 Oct 3;309(4):980-5.
- PubMed ID
- 13679070 [ View in PubMed]
- 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.