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PMID:16151013
| Citation |
Chipuk, JE, Bouchier-Hayes, L, Kuwana, T, Newmeyer, DD and Green, DR (2005) PUMA couples the nuclear and cytoplasmic proapoptotic function of p53. Science 309:1732-5 |
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| Abstract |
The Trp53 tumor suppressor gene product (p53) functions in the nucleus to regulate proapoptotic genes, whereas cytoplasmic p53 directly activates proapoptotic Bcl-2 proteins to permeabilize mitochondria and initiate apoptosis. Here, we demonstrate that a tripartite nexus between Bcl-xL, cytoplasmic p53, and PUMA coordinates these distinct p53 functions. After genotoxic stress, Bcl-xL sequestered cytoplasmic p53. Nuclear p53 caused expression of PUMA, which then displaced p53 from Bcl-xL, allowing p53 to induce mitochondrial permeabilization. Mutant Bcl-xL that bound p53, but not PUMA, rendered cells resistant to p53-induced apoptosis irrespective of PUMA expression. Thus, PUMA couples the nuclear and cytoplasmic proapoptotic functions of p53. |
| Links |
PubMed Online version:10.1126/science.1114297 |
| Keywords |
Animals; Apoptosis; Apoptosis Regulatory Proteins; Cell Line, Tumor; Cell Nucleus/metabolism; Cells, Cultured; Cytoplasm/metabolism; DNA Damage; Gene Expression Regulation; Humans; Immunoprecipitation; Mice; Mice, Inbred C57BL; Mitochondria/metabolism; Models, Biological; Permeability; Protein Binding; Protein Structure, Tertiary; Proto-Oncogene Proteins/metabolism; Proto-Oncogene Proteins c-bcl-2/metabolism; Recombinant Proteins/metabolism; Tumor Suppressor Protein p53/metabolism; Tumor Suppressor Proteins/chemistry; Tumor Suppressor Proteins/metabolism; Ultraviolet Rays; 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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