Gankyrin: an intriguing name for a novel regulator of p53 and RB.

The RB and p53 tumor suppressors lie at the heart of cancer biology, and inactivation of both pathways is seemingly essential for tumor development. Previous studies identified gankyrin as a component of the 26S proteasome that is consistently overexpressed in liver cancer and promotes cell transformation by binding RB. In the current issue of Cancer Cell, Fujita and colleagues (Higashitsuji et al., 2005) show that gankyrin also binds MDM2 and facilitates its destruction of p53. These important findings implicate gankyrin as a dual-purpose negative regulator of RB and p53, thereby identifying gankyrin as a rational cancer therapeutic target.