TRAF6 is required for BLyS-mediated NF-κB signaling in multiple myeloma cells.
Tumor necrosis factor receptor-associated factor 6 (TRAF6) transduces signals from members of the IL-1R/TLR and TNFR superfamilies to the transcription factors NF-κB and AP1. Elevated expression of the TNF family member B-lymphocyte stimulator (BLyS) in multiple myeloma (MM) has been described recently. However, the precise process by which BLyS signals in myeloma cell remains unknown. Here, we identified increased expression of TRAF6 in MM patient cells and the MM cell lines U266, RPMI8226, and KM3. Furthermore, rhBLyS induced TRAF6 up-regulation in these cells in a dose-dependent manner. Both the classical and alternative NF-κB pathways were activated by rhBLyS treatment. Depletion of TRAF6 by siRNA decreased levels of p-p65 and p-p100, even after stimulation with rhBLyS. Down-regulation of TRAF6 also abrogated rhBLyS-mediated cell viability. These findings suggest that TRAF6 is required for BLyS-mediated NF-κB signaling in myeloma cells and is a potential molecular therapeutic target in MM.
Affiliated Hospital of Nantong University, Department of Hematology, Nantong, 226001, Jiangsu, China.
Xinfeng
X
Wang
Jingjing
J
Wang
Hong
H
Liu
Ruirong
R
Xu
Runsheng
R
Ding
Shenhua
S
Jiang
Xudong
X
Wang
Hongming
H
Huang
D000328:Adult; D000368:Aged; D053264:B-Cell Activating Factor / Q000378:metabolism*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D034741:RNA, Small Interfering; D015398:Signal Transduction; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism*; D014162:Transfection
D053264:B-Cell Activating Factor; D016328:NF-kappa B; D034741:RNA, Small Interfering; D048029:TNF Receptor-Associated Factor 6; C505719:TNFSF13B protein, human