Nicole Rieth , Monika Hofstetter
نویسندگان
چکیده
Tissue inhibitor of metalloproteinase 1 (TIMP1) controls matrix metalloproteinase activity through 1:1 stoichiometric binding. Human TIMP-1 fused to a glycosylphosphatidylinositol (GPI) anchor (TIMP-1 GPI) shifts the activity of TIMP-1 from the extracellular matrix to the cell surface. TIMP-1 GPI treated renal cell carcinoma cells show increased apoptosis and reduced proliferation. Transcriptomic profiling and regulatory pathway mapping were used to identify the potential mechanisms driving these effects. Significant changes in the DNA binding inhibitors, TGFβ 1/SMAD and BMP pathways resulted from TIMP-1 GPI treatment. These events were linked to reduced TGFβ 1 signaling mediated by inhibition of proteolytic processing of latent TGFβ 1 by TIMP-1 GPI.
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Exogenous application of recombinant TIMP-1 protein modified by addition of a glycosylphosphatidylinositol (GPI) anchor allows efficient insertion of the fusion protein into cell membranes. This 'cell surface engineering' leads to changes in the proteolytic environment. TIMP-1-GPI shows enhanced as well as novel in vitro biological activities including suppression of proliferation, reduced migr...
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Tissue inhibitor of metalloproteinase 1 (TIMP-1) controls matrix metalloproteinase activity through 1:1stoichiometric binding. Human TIMP-1 fused to a glycosylphosphatidylinositol(GPI) anchor (TIMP-1 - GPI) shifts the activity of TIMP-1 from the extracellular matrix to the cell surface. TIMP-1 - GPI treated renal cell carcinoma cells show increased apoptosis and reduced proliferation.Transcript...
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