title: 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-x(L) 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 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.
authors.affiliation: Yorkshire Cancer Research P53 Laboratory, Department of Biology, University of York, York YO10 5DD, UK.
authors.forename: Ming
authors.initials: M
authors.lastname: Jiang
authors.forename: Jo
authors.initials: J
authors.lastname: Milner
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D053143:Caspase 2; D020169:Caspases / Q000378:metabolism; D003001:Cloning, Molecular; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology*; D016158:Genes, p53; D006801:Humans; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics*; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
chemical_list: C494826:BAX protein, human; C494811:BCL2L1 protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D053143:Caspase 2; D020169:Caspases