MT1-MMP Inhibits the Activity of Bst-2 via Their Cytoplasmic Domains Dependent Interaction
AbstractBst-2 (bone marrow stromal cell antigen 2) is a type II membrane protein, and it acts as a tetherin to inhibit virion releasing from infectious cells. Membrane type-1 matrix metalloproteinase (MT1-MMP) is a protease. It plays a pivotal role in cellular growth and migration by activating proMMP-2 into active MMP2. Our results here elaborate that MT1-MMP inhibits the tetherin activity of Bst-2 by interacting with Bst-2, and the cytoplasmic domains of both Bst-2 and MT1-MMP play critical roles within this interaction. Based on our experimental data, the assays for virion release and co-immunoprecipitation have clearly demonstrated that the activity of Bst-2 is markedly inhibited by MT1-MMP via their interaction; and both the N-terminal domain of Bst-2 and the C-terminal domain of MT1-MMP are important in the interaction. Immunostaining and Confocal Microscopy assay shows that MT1-MMP interacts with Bst-2 to form granular particles trafficking into cytoplasm from membrane and, finally, results in Bst-2 and MT1-MMP both being inhibited. In addition, mutant experiments elucidate that the N-terminal domain of Bst-2 is not only important in relating to the activity of Bst-2 itself, but is important for inhibiting the 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 also indicate that both the N-terminal domain of Bst-2 and the C-terminal domain of MT1-MMP are crucial in down-regulation. View Full-Text
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Fan, L.; Liu, L.; Zhu, C.; Zhu, Q.; Lu, S.; Liu, P. MT1-MMP Inhibits the Activity of Bst-2 via Their Cytoplasmic Domains Dependent Interaction. Int. J. Mol. Sci. 2016, 17, 818.
Fan L, Liu L, Zhu C, Zhu Q, Lu S, Liu P. MT1-MMP Inhibits the Activity of Bst-2 via Their Cytoplasmic Domains Dependent Interaction. International Journal of Molecular Sciences. 2016; 17(6):818.Chicago/Turabian Style
Fan, Long; Liu, Li; Zhu, Cuicui; Zhu, Qingyi; Lu, Shan; Liu, Ping. 2016. "MT1-MMP Inhibits the Activity of Bst-2 via Their Cytoplasmic Domains Dependent Interaction." Int. J. Mol. Sci. 17, no. 6: 818.
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