Bcl-2 constitutively suppresses p53-dependent apoptosis in colorectal cancer cells

Abstract

To dissect apoptotic genes governing the survival of colorectal carcinoma cells, we employed RNAi to silence Bcl-2 and Bcl-xLin isogenic clones ofp53+/+ andp53−/− cells, and ofBax+/− andBax−/− cells. We identify a novel proapoptotic function of p53 that does not require activation by genotoxic agents and that appears to be constitutively suppressed by Bcl-2. Silencing ofBcl-2induced massive p53-dependent apoptosis. The “Bcl-2/p53 axis” requires Bax and caspase 2 as essential apoptotic mediators. This newly discovered Bcl-2/p53 functional interface represents a key regulator of apoptosis which can be activated by targeting Bcl-2 in colorectal carcinoma cells.