Human CARD4 protein is a novel CED-4/Apaf-1 cell death family member that activates NF-kappa B

The nematode CED-4 protein and its human homolog Apaf-1 play a central role in apoptosis by functioning as direct activators of death-inducing caspase s. A novel human CED-4/Apaf-1 family member called CARD4 was identified tha t has a domain structure strikingly similar to the cytoplasmic, receptor-li ke proteins that mediate disease resistance in plants. CARD4 interacted wit h the serine-threonine kinase RICK and potently induced NF-kappa B activity through TRAF-6 and NIK signaling molecules. In addition, coexpression of C ARD4 augmented caspase-9-induced apoptosis. Thus, CARD4 coordinates downstr eam NF-kappa B and apoptotic signaling pathways and may be a component of t he host innate immune response.