Induction of nuclear factor kappaB 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 kappaB (NF-kappaB) transcription factor. In this study, we define the domains in CD30 which are required for NF-kappaB activation. Two separate elements of the cytoplasmic domain which were capable of inducing NF-kappaB independently of one another were identified. The first domain (domain 1) mapped to a approximately 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-kappaB activation through domain 2 but not domain 1. NF-kappaB induction through domain 2 was inhibited by coexpression of either full-length TRAF3 or dominant negative forms of TRAF1 or TRAF2. In contrast, NF-kappaB 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-kappaB by both TRAF-dependent and -independent mechanisms. TRAF-dependent induction of NF-kappaB appears to be regulated by the relative levels of individual TRAF proteins in the cell.
Duckett
C S
CS
Department of Medicine, University of Chicago, Illinois 60637, USA.
Gedrich
R W
RW
Gilfillan
M C
MC
Thompson
C B
CB
D000818:Animals; D018106:CD28 Antigens / Q000235:genetics; D002460:Cell Line; D006801:Humans; D017730:Ki-1 Antigen / Q000235:genetics*; D008156:Luciferases / Q000235:genetics; D051379:Mice; D016328:NF-kappa B / Q000502:physiology*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins; D017384:Sequence Deletion; D015398:Signal Transduction / Q000502:physiology*; D047990:TNF Receptor-Associated Factor 1; D047992:TNF Receptor-Associated Factor 2; D048008:TNF Receptor-Associated Factor 3
D018106:CD28 Antigens; D017730:Ki-1 Antigen; D016328:NF-kappa B; D011506:Proteins; D011993:Recombinant Fusion Proteins; D047990:TNF Receptor-Associated Factor 1; D047992:TNF Receptor-Associated Factor 2; D048008:TNF Receptor-Associated Factor 3; D008156:Luciferases