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  • Title: The von Hippel-Lindau tumor suppressor protein: new insights into oxygen sensing and cancer.
    Author: Kim W, Kaelin WG.
    Journal: Curr Opin Genet Dev; 2003 Feb; 13(1):55-60. PubMed ID: 12573436.
    Abstract:
    The von Hippel-Lindau tumor suppressor protein (pVHL) is the substrate-recognition module of an E3 ubiquitin ligase that targets the alpha subunits of hypoxia-inducible factor (HIF) for degradation in the presence of oxygen. Recognition of HIF by pVHL is linked to enzymatic hydroxylation of conserved prolyl residues in the HIF alpha subunits by members of the EGLN family. Dysregulation of HIF-target genes such as vascular endothelial growth factor and transforming growth factor alpha has been implicated in the pathogenesis of renal cell carcinomas and of hemangioblastomas, both of which frequently lack pVHL function.
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