NF-kappa B is a highly pleiotropic group of transcriptional factors that regulate a wide range of genes, mainly participating in immune defense and development. All members of the TNF receptor family activate these transcriptional factors, each with different functional consequences. Some promote adaptive immunity, and others, innate immunity;
While exploring the sequence of protein-protein interactions initiated by the death receptor Fas (CD95), we discovered an adapter protein, FADD/Mort1. This protein associates with death receptors and recruits MACH/caspase-8, a member of the caspase cysteine protease family that plays a crucial role in all apoptotic processes. We also discovered the protein cFLIP/CASH, a Caspase-8 homologue that serves as a biological inhibitor of death induction and initiator of non-apoptotic effects of the receptors. Both genetic screens and protein-purification approaches are applied to isolate regulatory proteins that associate with Caspase-8 and cFLIP/CASH.