[PDF][PDF] Inhibition of HIF is necessary for tumor suppression by the von Hippel-Lindau protein

K Kondo, J Klco, E Nakamura, M Lechpammer… - Cancer cell, 2002 - cell.com
K Kondo, J Klco, E Nakamura, M Lechpammer, WG Kaelin
Cancer cell, 2002cell.com
Inactivation of the von Hippel-Lindau tumor suppressor gene is linked to the development of
hereditary (VHL Disease-associated) and sporadic clear cell carcinoma of the kidney. The
VHL gene product, pVHL, targets the heterodimeric transcription factor HIF for
polyubiquitination, and restoration of pVHL function in VHL−/− renal carcinoma cells
suppresses their ability to form tumors in nude mice. Here we show that tumor suppression
by pVHL can be overridden by a HIF variant that escapes pVHL control. These studies prove …
Abstract
Inactivation of the von Hippel-Lindau tumor suppressor gene is linked to the development of hereditary (VHL Disease-associated) and sporadic clear cell carcinoma of the kidney. The VHL gene product, pVHL, targets the heterodimeric transcription factor HIF for polyubiquitination, and restoration of pVHL function in VHL−/− renal carcinoma cells suppresses their ability to form tumors in nude mice. Here we show that tumor suppression by pVHL can be overridden by a HIF variant that escapes pVHL control. These studies prove that HIF is a critical downstream target of pVHL and establish that activation of HIF target genes can promote tumorigenesis in vivo.
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