p53-dependent apoptosis pathways.
The p53 tumor suppressor limits cellular proliferation by inducing cell cycle arrest and apoptosis in response to cellular stresses such as DNA damage, hypoxia, and oncogene activation. Many apoptosis-related genes that are transcriptionally regulated by p53 have been identified. These are candidates for implementing p53 effector functions. In response to oncogene activation, p53 mediates apoptosis through a linear pathway involving bax transactivation, Bax translocation from the cytosol to membranes, cytochrome c release from mitochondria, and caspase-9 activation, followed by the activation of caspase-3, -6, and -7. p53-mediated apoptosis can be blocked at multiple death checkpoints, by inhibiting p53 activity directly, by Bcl-2 family members regulating mitochondrial function, by E1B 19K blocking caspase-9 activation, and by caspase inhibitors. Understanding the mechanisms by which p53 induces apoptosis, and the reasons why cell death is bypassed in transformed cells, is of fundamental importance in cancer research, and has great implications in the design of anticancer therapeutics.
Shen
Y
Y
Howard Hughes Medical Institute, Rutgers University, Piscataway, New Jersey 08854, USA.
White
E
E
D017209:Apoptosis / Q000502:physiology*; D061945:Caspase Inhibitors; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005786:Gene Expression Regulation; D015316:Genetic Therapy; D006801:Humans; D009369:Neoplasms / Q000628:therapy*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D020169:Caspases