Loss of pVHL is sufficient to cause HIF dysregulation in primary cells but does not promote tumor growth.

摘要: Inactivation of the von Hippel-Lindau (VHL) gene is associated with development highly vascularized tumors. pVHL targets alpha subunits hypoxia inducible factor (HIF) for ubiquitin-mediated degradation in an oxygen-dependent manner. Although pVHL-deficient tumor cell lines demonstrate constitutive stabilization and activation HIF, it has yet to be shown that loss murine Vhl alone sufficient dysregulate HIF. We utilized a genetic approach not only stabilize HIF-alpha under normoxia, but also fully activate HIF-mediated responses. These studies have implications hierarchy signaling events leading HIF stabilization, nuclear translocation, target expression. further does promote teratocarcinoma growth, indicating other changes must occur facilitate Vhl-mediated tumorigenesis.