title: The von Hippel-Lindau tumor suppressor protein is required for proper assembly of an extracellular fibronectin matrix.
abstract: 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.
authors.affiliation: Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
authors.forename: M
authors.initials: M
authors.lastname: Ohh
authors.forename: R L
authors.initials: RL
authors.lastname: Yauch
authors.forename: K M
authors.initials: KM
authors.lastname: Lonergan
authors.forename: J M
authors.initials: JM
authors.lastname: Whaley
authors.forename: A O
authors.initials: AO
authors.lastname: Stemmer-Rachamimov
authors.forename: D N
authors.initials: DN
authors.lastname: Louis
authors.forename: B J
authors.initials: BJ
authors.lastname: Gavin
authors.forename: N
authors.initials: N
authors.lastname: Kley
authors.forename: W G
authors.initials: WG
authors.lastname: Kaelin
authors.forename: O
authors.initials: O
authors.lastname: Iliopoulos
mesh_terms: D000818:Animals; D002461:Cell Line, Transformed; D004622:Embryo, Mammalian / Q000737:chemistry / Q000378:metabolism; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism*; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism*; D016147:Genes, Tumor Suppressor; D006801:Humans; D008025:Ligases; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation / Q000235:genetics; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein
chemical_list: D005353:Fibronectins; D011506:Proteins; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D008025:Ligases; C497446:VHL protein, human