The von Hippel-Lindau Tumor Suppressor Protein Is Required for Proper Assembly of an Extracellular Fibronectin Matrix
Copyright policy )The von Hippel-Lindau Tumor Suppressor Protein Is Required for Proper Assembly of an Extracellular Fibronectin Matrix
Fibronectin coimmunoprecipitated with wild-type von Hippel-Lindau protein (pVHL) but not tumor-derived pVHL mutants. Immunofluorescence and biochemical fractionation experiments showed that fibronectin colocalized with a fraction of pVHL associated with the endoplasmic reticulum, and cold competition experiments suggested that complexes between fibronectin and pVHL exist in intact cells. Assembly of an extracellular fibronectin matrix by VHL-/- renal carcinoma cells, as determined by immunofluorescence and ELISA assays, was grossly defective compared with VHL+/+ renal carcinoma cells. Reintroduction of wildtype, but not mutant, pVHL into VHL-/- renal carcinoma cells partially corrected this defect. Finally, extracellular fibronectin matrix assembly by VHL-/- mouse embryos and mouse embryo fibroblasts (MEFs), unlike their VHL+/+ counterparts, was grossly impaired. These data support a direct role of pVHL in fibronectin matrix assembly.
- Harvard University United States
- Dana-Farber Cancer Institute United States
- Bristol-Myers Squibb (Germany) Germany
- Howard Hughes Medical Institute United States
Tumor Suppressor Proteins, Ubiquitin-Protein Ligases, Proteins, Cell Biology, Embryo, Mammalian, Mice, Mutant Strains, Extracellular Matrix, Fibronectins, Ligases, Mice, Von Hippel-Lindau Tumor Suppressor Protein, Mutation, Tumor Cells, Cultured, Animals, Humans, Genes, Tumor Suppressor, Molecular Biology, Cell Line, Transformed, Protein Binding
Tumor Suppressor Proteins, Ubiquitin-Protein Ligases, Proteins, Cell Biology, Embryo, Mammalian, Mice, Mutant Strains, Extracellular Matrix, Fibronectins, Ligases, Mice, Von Hippel-Lindau Tumor Suppressor Protein, Mutation, Tumor Cells, Cultured, Animals, Humans, Genes, Tumor Suppressor, Molecular Biology, Cell Line, Transformed, Protein Binding
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