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-xL in isogenic clones of p53+/+ and p53-/cells, and of Bax+/- and Bax-/-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 of Bc-2 induced 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.