CD30 TNF RECEPTOR-ASSOCIATED FACTOR INTERACTION - NF-KAPPA-B ACTIVATION AND BINDING-SPECIFICITY/

CD30 is a member of the tumor necrosis factor (TNF) receptor superfami ly, CD30 is expressed on normal activated lymphocytes, on several vira lly transformed T- or B-cell lines and on neoplastic cells of Hodgkin' s lymphoma, The interaction of CD30 with its ligand induces pleiotropi c effects on cells resulting in proliferation, differentiation, or dea th, The CD30 cytoplasmic tail interacts with TNF receptor-associated f actors (TRAFs), which have been shown to transduce signals mediated by TNF-R2 and CD40, We demonstrate here that TRAF2 also plays an importa nt role in CD30-induced NF-kappa B activation, We also show that TRAF2 -mediated activation of NF-kappa B plays a role in the activation of H IV transcription induced by CD30 cross-linking, Detailed site-directed mutagenesis of the CD30 cytoplasmic tail reveals that there are two i ndependent binding sites for TRAF, each interacting with a different d omain of TRAF, Furthermore, we localized the TRAF-C binding site in CD 30 to a 5-7 amino acid stretch.