The regulation of BLyS expression levels through MAPK signal pathway in multiple myeloma / 中华微生物学和免疫学杂志

ObjectiveTo investigate the activation of MAPK signal pathway in multiple myeloma and the regulation of BLyS expression levels through MAPK signal pathway; preliminarily study the role of MAPK signal pathway in the up-regulation of BLyS expression levels induced by IFN-γ.MethodsActivated MAPK pathway were detected by Western blot,while the expression of BLyS were detected with RT-PCR and Western blot,and Western blot investigated the effect of MAPK pathway on BLyS expression levels induced by IFN-γ.ResultsIn addition to the expression of ERK,JNK,p38,p-JNK was also expressed in MM cell lines,the MAPK pathway inhibitor targeting JNK SP600125 can down-regulate the expression of BLyS,and its activator anisomycin can up-regulate the expression of BLyS.SP600125 restrained the proliferation and survival of MM cells.ConclusionJNK/SAPK pathway was activated in MM cells; The activated degree of JNK/SAPK pathway and the expression level of BLyS was positively correlated.JNK/SAPK pathway play an important role in the up-regulation of BLyS expression levels induced by IFN-γ.

Prokaryotic Expression of eBCMA-Fc Fusion Protein, a Soluble BLyS Receptor, with Computer-aided Molecular Design in E. coli / 中国生物化学与分子生物学报

B cell maturation antigen (BCMA) is a receptor of B lymphocyte stimulator (BLyS). Human IgG1Fc fusion proteins with the extracellular domain of BCMA(eBCMA), also called decoy receptors, have beenused as a potential BLyS antagonists to block BLyS activities. In order to design novel BLyS antagonistpeptides, computer-aided homologue modeling was used to construct an eBCMA-Fc fusion protein based on thecrystal structures of BCMA and Fc fragmant. To ensure the activity of eBCMA not to be interfered by Fcfusion, the root mean square distance (RMSD) for eBCMA and Fc were calculated to be 0.036 nm and 0.064nm, respectively, based on molecular docking modeling. An eBCMA-Fc fusion gene was constructed andintroduced into E. coli for expression. As expected, the purified 36 kD eBCMA-Fc fusion protein was able tobind BLyS in vitro at a dosage-dependent manner and demonstrated an anti-proliferative activity induced byBLyS in Daudi cells. The results have provided useful information on the evaluation of computer modeling andthe in vitro biological activity for the design of potential BLyS antagonist peptides.