The von Hippel-Lindau gene, kidney cancer, and oxygen sensing.
Recent studies of a relatively rare hereditary cancer syndrome, von Hippel-Lindau (VHL) disease, have shed new light on the molecular pathogenesis of kidney cancer and, perhaps more important, on how mammalian cells sense and respond to changes in oxygen availability. This knowledge is already translating into new therapeutic targets for kidney cancer as well as for multiple conditions, such as myocardial infarction and stroke, in which ischemia plays a pathogenic role. This review summarizes the current knowledge of the molecular pathogenesis of von Hippel-Lindau disease and the role of the VHL gene product (pVHL) in kidney cancer and the mammalian oxygen sensing pathway.
Kaelin
William G
WG
Howard Hughes Medical Institute, Dana-Farber Cancer Institute, and Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. william_kaelin@dfci.harvard.edu
D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology; D006801:Humans; D007680:Kidney Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D006623:von Hippel-Lindau Disease / Q000235:genetics*
D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human