Laboratory Medicine Center, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, People's Republic of China.
Mol Cell Biochem. 2011 Nov;357(1-2):21-30. doi: 10.1007/s11010-011-0871-9. Epub 2011 May 24.
B-lymphocyte stimulator (BAFF) is a recently recognized member of the tumor necrosis factor ligand family (TNF) and a potent cell-survival factor expressed in many hematopoietic cells. BAFF regulates B-cell survival, differentiation, and proliferation by binding to three TNF receptors: TACI, BCMA, and BAFF-R. The mechanism involved in BAFF-R gene expression and regulation remains elusive. In this study, we examined BAFF-R gene expression, function, and regulation in multiple myeloma (KM3) cells. It was found that BAFF-BAFF-R induced cell survival by activating NF-κB1 pathway and NF-κB2 pathway. It was also found that NF-κB was an important transcription factor involved in regulating BAFF-R expression through one NF-κB binding site in the BAFF-R promoter, suggesting that inhibiting NF-κB could decrease the expression of BAFF-R mRNA and protein, and promote activity of BAFF-R gene. Our findings indicate that both NF-κB pathways are involved in the regulation of BAFF-R gene and the NF-κB-binding site of BAFF-R may be a new therapeutic target in this disease.
B 淋巴细胞刺激因子（BAFF）是肿瘤坏死因子配体家族（TNF）的一个新成员，也是许多造血细胞中表达的一种有效的细胞存活因子。BAFF 通过与三个 TNF 受体：TACI、BCMA 和 BAFF-R 结合，调节 B 细胞的存活、分化和增殖。BAFF-R 基因表达和调控的机制仍不清楚。在这项研究中，我们研究了多发性骨髓瘤（KM3）细胞中 BAFF-R 基因的表达、功能和调控。结果发现，BAFF-BAFF-R 通过激活 NF-κB1 途径和 NF-κB2 途径诱导细胞存活。还发现 NF-κB 是一个重要的转录因子，通过 BAFF-R 启动子中的一个 NF-κB 结合位点参与调节 BAFF-R 表达，提示抑制 NF-κB 可以降低 BAFF-R mRNA 和蛋白的表达，并促进 BAFF-R 基因的活性。我们的研究结果表明，两条 NF-κB 途径都参与了 BAFF-R 基因的调控，BAFF-R 的 NF-κB 结合位点可能是该疾病的一个新的治疗靶点。
