Reference : Membrane Type 1 Matrix Metalloproteinase-Associated Degradation of Tissue Inhibitor of M...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/12731
Membrane Type 1 Matrix Metalloproteinase-Associated Degradation of Tissue Inhibitor of Metalloproteinase 2 in Human Tumor Cell Lines
English
Maquoi, Erik mailto [Université de Liège - ULg > Département des sciences cliniques > Labo de biologie des tumeurs et du développement >]
Frankenne, Francis [> >]
Baramova, Eugénia [> > > >]
Munaut, Carine mailto [Université de Liège - ULg > Département des sciences cliniques > Labo de biologie des tumeurs et du développement >]
Sounni, Nor Eddine mailto [Université de Liège - ULg > Département des sciences cliniques > Labo de biologie des tumeurs et du développement >]
Remacle, Albert [> >]
Noël, Agnès mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme >]
Murphy, Gillian [> > > >]
Foidart, Jean-Michel mailto [Université de Liège - ULg > Département des sciences cliniques > Gynécologie - Obstétrique >]
14-Apr-2000
Journal of Biological Chemistry
American Society for Biochemistry and Molecular Biology
275
15
11368-78
Yes (verified by ORBi)
International
0021-9258
1083-351X
Baltimore
MD
[en] Tissue inhibitor of metalloproteinase 2 (TIMP-2) is required for the membrane type 1 matrix metalloproteinase (MT1-MMP)-dependent activation of pro-MMP-2 on the cell surface. MT1-MMP-bound TIMP-2 has been shown to function as a receptor for secreted pro-MMP-2, resulting in the formation of a trimolecular complex. In the presence of uncomplexed active MT1-MMP, the prodomain of cell surface-associated MMP-2 is cleaved, and activated MMP-2 is released. However, the behavior of MT1-MMP-bound TIMP-2 during MMP-2 activation is currently unknown. In this study, (125)I-labeled recombinant TIMP-2 ((125)I-rTIMP-2) was used to investigate the fate of TIMP-2 during pro-MMP-2 activation by HT1080 and transfected A2058 cells. HT1080 and A2058 cells transfected with MT1-MMP cDNA (but not vector-transfected A2058 cells) were able to bind (125)I-rTIMP-2, to activate pro-MMP-2, and to process MT1-MMP into an inactive 43-kDa form. Under these conditions, (125)I-rTIMP-2 bound to the cell surface was rapidly internalized and degraded in intracellular organelles through a bafilomycin A(1)-sensitive mechanism, and (125)I-bearing low molecular mass fragment(s) were released in the culture medium. These different processes were inhibited by hydroxamic acid-based synthetic MMP inhibitors and rTIMP-2, but not by rTIMP-1 or cysteine, serine, or aspartic proteinase inhibitors. These results support the concept that the MT1-MMP-dependent internalization and degradation of TIMP-2 by some tumor cells might be involved in the regulation of pericellular proteolysis.
http://hdl.handle.net/2268/12731

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