c-E10 Is a Caspase-recruiting Domain-containing Protein That Interacts with Components of Death Receptors Signaling Pathway and Activates Nuclear Factor-κB*

Members of the tumor necrosis factor receptor superfamily induce apoptosis via interaction with FADD and regulate cell growth and differentiation through TRADD and TRAFs molecules. While screening for molecules involved in the regulation of death receptor signaling, we identified a novel protein, c-E10. c-E10 contains an amino-terminal caspase-recruiting domain (CARD) and shares a sequence homologous with E10, a viral CARD-containing protein that binds to c-E10. In transfection experiments c-E10 oligomerizes, binds to the cytoplasmic portion of TRAIL receptor 1 (DR4) and coprecipitates with TRADD. Expression of c-E10 under the control of a doxycycline-dependent transcriptional transactivator results in NF-κB activation, which is inhibited by dominant negative forms of TRAF2 and NIK kinase. Thus, our results suggest that c-E10 is an adapter protein that activates NF-κB through a molecular pathway involved in death receptor signaling.