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PMID:14963330
| Citation |
Chipuk, JE, Kuwana, T, Bouchier-Hayes, L, Droin, NM, Newmeyer, DD, Schuler, M and Green, DR (2004) Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis. Science 303:1010-4 |
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| Abstract |
The tumor suppressor p53 exerts its anti-neoplastic activity primarily through the induction of apoptosis. We found that cytosolic localization of endogenous wild-type or trans-activation-deficient p53 was necessary and sufficient for apoptosis. p53 directly activated the proapoptotic Bcl-2 protein Bax in the absence of other proteins to permeabilize mitochondria and engage the apoptotic program. p53 also released both proapoptotic multidomain proteins and BH3-only proteins [Proapoptotic Bcl-2 family proteins that share only the third Bcl-2 homology domain (BH3)] that were sequestered by Bcl-xL. The transcription-independent activation of Bax by p53 occurred with similar kinetics and concentrations to those produced by activated Bid. We propose that when p53 accumulates in the cytosol, it can function analogously to the BH3-only subset of proapoptotic Bcl-2 proteins to activate Bax and trigger apoptosis. |
| Links |
PubMed Online version:10.1126/science.1092734 |
| Keywords |
Animals; Apoptosis; BH3 Interacting Domain Death Agonist Protein; Carrier Proteins/metabolism; Cell Line, Transformed; Cell Nucleus/metabolism; Cells, Cultured; Cytochromes c/metabolism; Cytosol/metabolism; Gene Expression Regulation; Genes, p53; HeLa Cells; Humans; Intracellular Membranes/physiology; Liposomes/metabolism; Mice; Mitochondria/physiology; Mutation; Permeability; Protein Conformation; Proto-Oncogene Proteins/chemistry; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins/metabolism; Proto-Oncogene Proteins c-bcl-2/metabolism; Recombinant Fusion Proteins/metabolism; Tumor Suppressor Protein p53/chemistry; Tumor Suppressor Protein p53/metabolism; Ultraviolet Rays; Wheat Germ Agglutinins/pharmacology; bcl-2-Associated X Protein; bcl-X Protein |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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References
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