| First Author | Seo SY | Year | 2004 |
| Journal | J Biol Chem | Volume | 279 |
| Issue | 40 | Pages | 42240-9 |
| PubMed ID | 15231831 | Mgi Jnum | J:93470 |
| Mgi Id | MGI:3057092 | Doi | 10.1074/jbc.M406775200 |
| Citation | Seo SY, et al. (2004) BAD is a pro-survival factor prior to activation of its pro-apoptotic function. J Biol Chem 279(40):42240-9 |
| abstractText | The mammalian BAD protein belongs to the BH3-only subgroup of the BCL-2 family. In contrast to its known pro-apoptotic function, we found that endogenous and overexpressed BAD(L) can inhibit cell death in neurons and other cell types. Several mechanisms regulate the conversion of BAD from an anti-death to a pro-death factor, including alternative splicing that produces the N-terminally truncated BAD(S). In addition, caspases convert BAD(L) into a pro-death fragment that resembles the short splice variant. The caspase site that is selectively cleaved during cell death following growth factor (interleukin-3) withdrawal is conserved between human and murine BAD. A second cleavage site that is required for murine BAD to promote death following Sindbis virus infection, gamma-irradiation, and staurosporine treatment is not conserved in human BAD, consistent with the inability of human BAD to promote death with these stimuli. However, loss of the BAD N terminus by any mechanism is not always sufficient to activate its pro-death activity, suggesting that the N terminus is a regulatory domain rather than an anti-death domain. These findings suggest that BAD is more than an inert death factor in healthy cells; it is also a pro-survival factor, prior to its role in promoting cell death. |
