Grant: Project Grant

Precise control of the levels for individual cellular proteins is essential for homeostasis and is achieved in part by the activity of a class of enzymes called ubiquitin ligases, which mark proteins for degradation. The von Hippel-Lindau (VHL) tumour suppressor forms an ubiquitin ligase that regulates proteins involved in the oxygen response. VHL is mutated in the majority of renal clear-cell carcinoma (RCC). We have identified a new target of VHL, the retinoblastoma protein (pRb). Moreover, we have found that loss of VHL in RCC causes an accumulation of pRb, resulting in the suppression of genes that could promote death. This proposal will determine the biological effects of pRb stabilization in RCC as well as the mechanisms that govern the unexpected connection between these two important tumour-suppressor proteins.