Blocking the CD40 pathway in Reed-Sternberg cells

. Shown is a schematic model of the roles for TRAF3 in CD40 signaling. TRAF3 has a membrane-associated role, interacting with the cytoplasmic tail of CD40.12-14,20 In the present study, we show a distinct role for TRAF3 in the cytoplasm, as an inhibitor of CD40 signaling in the resting state. A potential site for intervention to block CD40 signaling occurs in the cytoplasm at the point of proteolytic degradation of the TRAF3 molecule, which appears to be necessary for propagation of the signal from CD40 to NF-κB.