| First Author | Chipuk JE | Year | 2005 |
| Journal | Science | Volume | 309 |
| Issue | 5741 | Pages | 1732-5 |
| PubMed ID | 16151013 | Mgi Jnum | J:101198 |
| Mgi Id | MGI:3603103 | Doi | 10.1126/science.1114297 |
| Citation | Chipuk JE, et al. (2005) PUMA couples the nuclear and cytoplasmic proapoptotic function of p53. Science 309(5741):1732-5 |
| abstractText | 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. |
