Tumors with Nonfunctional Retinoblastoma Protein Are Killed by Reduced γ-Tubulin Levels

In various tumors inactivation of growth control is achieved by interfering with the RB1 signaling pathway. Here, we describe that RB1 and gamma-tubulin proteins moderate each other's expression by binding to their respective gene promoters. Simultaneous reduction of RB1 and gamma-tubulin protein levels results in an E2F1-dependent up-regulation of apoptotic genes such as caspase 3. We report that in various tumors types, there is an inverse correlation between the expression levels of gamma-tubulin and RB1 and that in tumor cell lines with a nonfunctioning RB1, reduction of gamma-tubulin protein levels leads to induction of apoptosis. Thus, the RB1/gamma- tubulin signal network can be considered as a new target for cancer treatment.