Insights into the role of the von Hippel-Lindau gene product. A key player in hypoxic regulation.
Many adaptive responses to hypoxia involve changes in gene transcription mediated by the hypoxia-inducible factor 1 complex. Central to this is oxygen-dependent proteolysis of the alpha subunit, which has recently been shown to require the von Hippel-Lindau tumour-suppressor protein. This observation provides one mechanism by which inherited defects in the von Hippel-Lindau gene could cause features of the clinical syndrome, and offers insight into the events leading to sporadic clear cell renal cancer. Furthermore, it clearly implicates the von Hippel-Lindau tumour-suppressor protein in the biochemistry of oxygen sensing.
Maxwell
P H
PH
Nephrology and Oxygen-Sensing Laboratory, Henry Wellcome Building of Genomic Medicine, Oxford, UK. pmaxwell@hammer.imm.ox.ac.uk
Pugh
C W
CW
Ratcliffe
P J
PJ
D004268:DNA-Binding Proteins / Q000235:genetics; D016147:Genes, Tumor Suppressor; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D000860:Hypoxia / Q000235:genetics; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D006623:von Hippel-Lindau Disease / Q000235:genetics*
D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D014157:Transcription Factors