TANK, A CO-INDUCER WITH TRAF2 OF TNF-MEDIATED AND CD40L-MEDIATED NF-KAPPA-B ACTIVATION

We describe a new signal mediator of NF-kappa B activation, TANK, that acts in a pathway common to two surface receptors CD40 and TNER II. T RAF family members interact directly with these receptors. Using the y east two-hybrid system, TANK was identified as an intracellular protei n without previous homologs that interacts with all three known TRAF f amily members. In cotransfection experiments, TANK and TRAE2 activate NF-kappa B synergistically, requiring both the amino-terminal portion of TANK and the ring finger domain of TRAF2. TANK has a negatively act ing carboxyl terminus and is constitutively inactive, but TRAE2 bindin g overcomes the internal inhibitory influence. We propose that ligand binding to CD40 or TNFR II leads to the formation of a TRAE2/TANK comp lex, mediating NP-kappa B activation.