TNFR-associated factor-3 is associated with BAFF-R and negatively regulates BAFF-R-mediated NF-kappa B activation and IL-10 production.
TALL-1 is a member of the TNF family that is critically involved in B cell survival, maturation, and progression of lupus-like autoimmune diseases. TALL-1 has three receptors, including BCMA, TACI, and BAFF-R, which are mostly expressed by B lymphocytes. Gene knockout studies have indicated that BAFF-R is the major stimulatory receptor for TALL-1 signaling and is required for normal B cell development. The intracellular signaling mechanisms of BAFF-R are not known. In this report, we attempted to identify BAFF-R-associated downstream proteins by yeast two-hybrid screening. This effort identified TNFR-associated factor (TRAF)3 as a protein specifically interacting with BAFF-R in yeast two-hybrid assays. Coimmunoprecipitation experiments indicated that BAFF-R interacts with TRAF3 in B lymphoma cells and this interaction is stimulated by TALL-1 treatment. Domain mapping experiments indicated that both a 6-aa membrane proximal region and the C-terminal 35 aa of BAFF-R are required for its interaction with TRAF3. Moreover, overexpression of TRAF3 inhibits BAFF-R-mediated NF-kappaB activation and IL-10 production. Taken together, our findings suggest that TRAF3 is a negative regulator of BAFF-R-mediated NF-kappaB activation and IL-10 production.
Xu
Liang-Guo
LG
Department of Immunology, National Jewish Medical and Research Center, University of Colorado Health Sciences Center, Denver, CO 80206, USA.
Shu
Hong-Bing
HB
D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000276:immunology; D015536:Down-Regulation / Q000276:immunology*; D006801:Humans; D016753:Interleukin-10 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D007424:Intracellular Fluid / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins / Q000502:physiology; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000276:immunology; D011506:Proteins / Q000378:metabolism / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology; D048008:TNF Receptor-Associated Factor 3; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D008565:Membrane Proteins; D016328:NF-kappa B; D011506:Proteins; D018124:Receptors, Tumor Necrosis Factor; D048008:TNF Receptor-Associated Factor 3; C435926:TNFRSF13C protein, human; C505719:TNFSF13B protein, human; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10