title: Two sides to every story: the HIF-dependent and HIF-independent functions of pVHL.
abstract: von Hippel-Lindau (VHL) disease is a hereditary cancer syndrome caused by inherited mutations that inactivate the VHL tumour suppressor gene. The VHL locus encodes pVHL, whose best studied function is to bind to and down-regulate the hypoxia-inducible factor (HIF) family of oxygen-dependent transcription factors. Early efforts have established the fundamental role of HIF in VHL-defective tumorigenesis and in particular renal cell carcinoma. However, recent findings have revealed an alternate side to the story, the HIF-independent tumour suppressor functions of pVHL. These include pVHL's ability to regulate apoptosis and senescence as well as its role in the maintenance of primary cilium and orchestrating the deposition of the extracellular matrix. To what extent these HIF-dependent and HIF-independent functions cooperate in VHL-defective tumorigenesis remains to be determined.
authors.affiliation: Departments of Medicine and Genetics, Division of Hematology/Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Mingqing
authors.initials: M
authors.lastname: Li
authors.forename: William Y
authors.initials: WY
authors.lastname: Kim
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000378:metabolism; D002923:Cilia / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000235:genetics / Q000378:metabolism*; D007680:Kidney Neoplasms / Q000378:metabolism; D051379:Mice; D008870:Microtubules / Q000378:metabolism; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics* / Q000378:metabolism*; D006623:von Hippel-Lindau Disease / Q000235:genetics*; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051793:Hypoxia-Inducible Factor 1; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D000099162:Endothelial PAS Domain-Containing Protein 1; C497446:VHL protein, human