title: MT1-MMP Inhibits the Activity of Bst-2 via Their Cytoplasmic Domains Dependent Interaction.
abstract: Bst-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.
authors.affiliation: Jiangsu Province Key Laboratory for Molecular and Medicine Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210023, China. fl891116@163.com.
authors.forename: Long
authors.initials: L
authors.lastname: Fan
authors.affiliation: Laboratory of Molecular Biology, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing 210029, China. jsszyyfz@126.com.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: Jiangsu Province Key Laboratory for Molecular and Medicine Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210023, China. zhu_ccyx_12@163.com.
authors.forename: Cuicui
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Department of Urology, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing 210029, China. zhuqy1971@126.com.
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Jiangsu Province Key Laboratory for Molecular and Medicine Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210023, China. lu_shan@hotmail.com.
authors.forename: Shan
authors.initials: S
authors.lastname: Lu
authors.affiliation: Jiangsu Province Key Laboratory for Molecular and Medicine Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210023, China. 08201@njnu.edu.cn.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004285:Dogs; D058851:GPI-Linked Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D061985:Madin Darby Canine Kidney Cells; D053511:Matrix Metalloproteinase 14 / Q000737:chemistry* / Q000378:metabolism*; D009154:Mutation; D011485:Protein Binding; D015398:Signal Transduction; D000074010:Bone Marrow Stromal Antigen 2
chemical_list: D015703:Antigens, CD; D058851:GPI-Linked Proteins; D053511:Matrix Metalloproteinase 14; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2; C507086:MMP14 protein, human
keywords: Membrane type-1 matrix metalloproteinase (MT1-MMP); bone marrow stromal cell antigen 2 (Bst-2); tetherin; virus release