TANK, a co-inducer with TRAF2 of TNF- and CD 40L-mediated NF-kappaB activation.
We describe a new signal mediator of NF-kappaB activation, TANK, that acts in a pathway common to two surface receptors CD40 and TNFR II. TRAF family members interact directly with these receptors. Using the yeast two-hybrid system, TANK was identified as an intracellular protein without previous homologs that interacts with all three known TRAF family members. In cotransfection experiments, TANK and TRAF2 activate NF-kappaB synergistically, requiring both the amino-terminal portion of TANK and the ring finger domain of TRAF2. TANK has a negatively acting carboxyl terminus and is constitutively inactive, but TRAF2 binding overcomes the internal inhibitory influence. We propose that ligand binding to CD40 or TNFR II leads to the formation of a TRAF2/TANK complex, mediating NF-kappaB activation.
Cheng
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Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA.
Baltimore
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D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019013:CD40 Antigens / Q000502:physiology*; D023201:CD40 Ligand; D002478:Cells, Cultured; D006801:Humans; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000502:physiology*; D011485:Protein Binding; D011506:Proteins / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D047992:TNF Receptor-Associated Factor 2; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D019013:CD40 Antigens; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D011506:Proteins; D018124:Receptors, Tumor Necrosis Factor; C484406:TANK protein, human; D047992:TNF Receptor-Associated Factor 2; C100814:Tank protein, mouse; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand