| First Author | Degenhardt K | Year | 2002 |
| Journal | J Biol Chem | Volume | 277 |
| Issue | 16 | Pages | 14127-34 |
| PubMed ID | 11836241 | Mgi Jnum | J:76058 |
| Mgi Id | MGI:2178486 | Doi | 10.1074/jbc.M109939200 |
| Citation | Degenhardt K, et al. (2002) Bax and Bak independently promote cytochrome C release from mitochondria. J Biol Chem 277(16):14127-34 |
| abstractText | Pro-apoptotic Bax and Bak have been implicated in the regulation of p53-dependent apoptosis. We assessed the ability of primary baby mouse kidney (BMK) epithelial cells from bax(-/-), bak(-/-), and bax(-/-) bak(-/-) mice to be transformed by E1A alone or in conjunction with dominant-negative p53 (p53DD). Although E1A alone transformed BMK cells from p53-deficient mice, E1A alone did not transform BMK cells from bax(-/-), bak(-/-), or bax(-/-) bak(-/-) mice. Thus, the loss of both Bax and Bak was not sufficient to relieve p53-dependent suppression of transformation in epithelial cells. To test the requirement for Bax and Bak in other death signaling pathways, stable E1A plus p53DD-transformed BMK cell lines were derived from the bax(-/-), bak(-/-), and bax(-/-) bak(-/-) mice and characterized for their response to tumor necrosis factor-alpha (TNF-alpha)-mediated apoptosis. The loss of both Bax and Bak severely impaired TNF-alpha-mediated apoptosis, but the presence of either Bax or Bak alone was sufficient for cell death. Cytochrome c was released from mitochondria, and caspase-9 was activated in Bax- or Bak-deficient cells in response to TNF-alpha but not in cells deficient in both. Thus, either Bax or Bak is required for death signaling through mitochondria in response to TNF-alpha, but both are dispensable for p53-dependent transformation inhibition. |
