摘要
Bst-2(骨髓基质细胞抗原-2)是一种II型膜蛋白,其主要功能是抑制病毒从感染细胞释放;基质金属蛋白酶-14(MT1-MMP)是一种膜蛋白酶,其主要功能是通过激活pro MMP2在细胞生长和迁移中扮演重要角色.本研究主要探讨了MT1-MMP抑制Bst-2生物活性的分子机制.实验结果表明,MT1-MMP通过与Bst-2相互作用进而抑制Bst-2的活性和功能;并且,在此相互作用中,这两种膜蛋白的细胞质结构域(Bst-2的N-末端结构域和MT1-MMP的C-末端结构域)起到了极为关键的作用.此外,还发现Bst-2的N-末端结构域在Bst-2抑制MT1-MMP活性的过程中也不可或缺.这些结果为临床上探索抑制病毒感染和肿瘤转移的新方法和新药物研制开发提供了理论依据.
Bst-2（bone marrow stromal cell antigen 2）is a type II membrane protein and acts as a tetherin to inhibit virion releasing from infectious cells. Membrane type-1 matrix metalloproteinase （MT1-MMP）is a protease and plays a pivotal role in cellular growth and migration by activating proMMP-2 into active MMP2. In this study, we explored the molecular mechanism of MT1-MMP inhibiting the activity of Bst-2. From experimental data, it＇ s elaborated that MT1-MMP inhibited the tetherin activity of Bst-2 via the interaction within, and the cytoplasmic domains of both Bst-2 and MT1- MMP play critical roles in the interaction. Furthermore, we found that that N-terminal domain of Bst-2 is not only important in relating to the activity of Bst-2 itself, but important for inhibiting the activities of MT1-MMP and MT1-MMP/ proMMP2/MMP2 pathway. These findings suggest that MT1-MMP is a novel inhibitor of Bst-2 in MT1-MMP expressed cell lines and indicate that both N-terminal domain of Bst-2 and C-terminal domain of MT1-MMP are crucial in their activity down-regulation.
出处
《南京师大学报（自然科学版）》
CAS
CSCD
北大核心
2016年第3期79-88,共10页
Journal of Nanjing Normal University(Natural Science Edition)
基金
国家自然科学基金(81272850
81172007
81472415)
