Inhibition of hypoxia-inducible factor is sufficient for growth suppression of VHL-/- tumors.

The von Hippel-Lindau tumor suppressor protein (pVHL) is a substrate receptor for the mammalian SCF-2 E3 ubiquitin ligase complex that targets several substrates for ubiquitination and proteasomal degradation. Among these targets are the alpha-regulatory subunits of the hypoxia-inducible factor (HIF). VHL-/- cells constitutively overexpress hypoxia-inducible genes through both transcriptional and posttranscriptional mechanisms and form tumors when injected into nude mice.