NF-kappaB activation in CD27 signaling: involvement of TNF receptor-associated factors in its signaling and identification of functional region of CD27.
CD27 belongs to TNF receptor family, and it is unique in this family for its disulfide-linked homodimerization of 55-kDa monomers. In the present study we demonstrate that overexpression of CD27 in 293 cells induces a low level of NF-kappaB activation, and the ligation of the receptor by its corresponding ligand (CD70) augments this signal dramatically. Either TNF receptor-associated factor-2 (TRAF2) or TRAF3 binds to the CD27 molecule from the coimmunoprecipitation experiment. This NF-kappaB activation signal is inhibited by dominant negative TRAF2 or intact TRAF3, indicating that TRAF2 and TRAF3 works as a mediator and an inhibitor, respectively. The activated NF-kappaB complex contains at least two components, p50 and p65, but not p52. All these phenomena have also been observed in the TNF receptor type II, CD30 and CD40 signaling system, indicating that this receptor family uses the common or similar molecules for this signal. Finally, we identified the 13-amino acid alignment in the cytoplasmic region of the CD27 molecule (residues 238-250 amino acids), which is critical for the NF-kappaB activation signal and also for its association with TRAFs. This amino acid alignment contains the EEEG sequence, which is essential for interaction of CD30 or CD40 with TRAFs (TRAF1 and TRAF2, but not TRAF3), and also contains the PIQED sequence, which is similar to PXQXT that is known to be necessary for interaction of TNF receptor II and CD30 with TRAFs (TRAF1, 2, and 3).
Yamamoto
H
H
Department of Medicine III, Osaka University Medical School, Japan.
Kishimoto
T
T
Minamoto
S
S
D000595:Amino Acid Sequence; D015703:Antigens, CD; D053282:CD27 Ligand; D002460:Cell Line; D019281:Dimerization; D005786:Gene Expression Regulation; D006801:Humans; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000502:physiology; D016328:NF-kappa B / Q000502:physiology*; D011506:Proteins / Q000502:physiology*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000502:physiology*; D047990:TNF Receptor-Associated Factor 1; D047992:TNF Receptor-Associated Factor 2; D048008:TNF Receptor-Associated Factor 3; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000737:chemistry / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D015703:Antigens, CD; D053282:CD27 Ligand; C505771:CD70 protein, human; D046911:Macromolecular Substances; D008565:Membrane Proteins; D016328:NF-kappa B; D011506:Proteins; D047990:TNF Receptor-Associated Factor 1; D047992:TNF Receptor-Associated Factor 2; D048008:TNF Receptor-Associated Factor 3; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D014409:Tumor Necrosis Factor-alpha