Induction of nuclear factor kappa B by the CD30 receptor is mediated by TRAF1 and TRAF2

CD30 is a lymphoid cell-specific surface receptor which was originally identified as an antigen expressed on Hodgkin's lymphoma cells, Activation of CD30 induces the nuclear factor kappa B (NF-kappa B) transcription factor, In this study, we define the domains in CD30 which are required for NF-kappa B activation, Two separate elements of the cytoplasmic domain which were capable of inducing NF-kappa B independently of one another were identified. The first domain (domain 1) mapped to a similar to 120-amino-acid sequence in the membrane-proximal region of the CD30 cytoplasmic tail, between residues 410 and 531, A second, more carboxy-terminal region (domain 2) was identified between residues 553 and 595, Domain 2 contains two 5- to 10-amino-acid elements which can mediate the binding of CD30 to members of the tumor necrosis factor receptor-associated factor (TRAF) family of signal transducing proteins, Coexpression of CD30 with TRAF1 or TRAF2 but not TRAF3 augmented NF-kappa B activation through domain 2 but not domain 1, NF-KB induction through domain 2 was inhibited by coexpression of either full-length TRAF3 or dominant negative forms of TRAF1 or TRAF2, In contrast, NF-kappa B induction by domain 1 was not affected by alterations in TRAF protein levels, Together, these data support a model in which CD30 can induce NF-kappa B by both TRAF-dependent and -independent mechanisms, TRAF-dependent induction of NF-KB appears to be regulated by the relative levels of individual TRAF proteins in the cell.