VHL is a tumor suppressor and the substrate recognition component of an E3 ubiquitin ligase that targets HIF-1α for polyubiquitination and rapid proteasomal degradation.34,35Vhl KO by Ad-CRE infection stabilized HIF-1α and increased gene expression for glycolysis and collagen cross-linking enzymes (Fig. 3i, j). This evidence concerns the gene HIF1A and neoplasm.