VHL and renal cell carcinoma: In VHL-defective renal carcinoma cells (RCC), inactivation of HIF-α proteolysis upregulates both HIF-1α and HIF-2α with global induction of HIF target gene expression (Maxwell et al, 1999), stimulating investigations of the role of the HIF pathway in tumour development (Maranchie et al, 2002; Kondo et al, 2002, 2003; Zimmer et al, 2004; Raval et al, 2005).