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

Ming Jiang; Jo Milner

doi:10.1101/gad.252603

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

Ming Jiang and
Jo Milner1

Yorkshire Cancer Research P53 Laboratory, Department of Biology, University of York, York YO10 5DD, UK

Abstract

To dissect apoptotic genes governing the survival of colorectal carcinoma cells, we employed RNAi to silence Bcl-2 and Bcl-x_Lin 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 Bcl-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.

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Footnotes

↵1 Corresponding author.
E-MAIL ajm24{at}york.ac.uk; FAX 01904-432808.
Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.252603.
- Received October 21, 2002.
- Accepted February 6, 2003.
Cold Spring Harbor Laboratory Press