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.