| First Author | Ottilie S | Year | 1997 |
| Journal | J Biol Chem | Volume | 272 |
| Issue | 49 | Pages | 30866-72 |
| PubMed ID | 9388232 | Mgi Jnum | J:44438 |
| Mgi Id | MGI:1100214 | Doi | 10.1074/jbc.272.49.30866 |
| Citation | Ottilie S, et al. (1997) Dimerization properties of human BAD. Identification of a BH-3 domain and analysis of its binding to mutant BCL-2 and BCL-XL proteins. J Biol Chem 272(49):30866-72 |
| abstractText | Bad, an inducer of programmed cell death, was recently isolated from a mouse cDNA library by its ability to bind to the anti-apoptotic protein BCL-2. Sequence analysis suggested that Bad was a member of the BCL-2 gene family that encodes both inducers and inhibitors of programmed cell death. To further analyze the role of BAD in the network of homo- and heterodimers formed by the BCL-2 family, we have cloned the human homologue of BAD and assessed its biological activity and its interactions with wild type and mutant BCL-2 family proteins. Our results indicate that the human BAD protein, like its mouse homologue, is able to induce apoptosis when transfected into mammalian cells. Furthermore, in yeast two-hybrid assays as well as quantitative in vitro interaction assays, human Bad interacted with BCL-2 and BCL-XL. Sequence alignments of human BAD revealed the presence of a BH-3 homology domain as seen in other BCL-2 family proteins. Peptides derived from this domain were able to completely inhibit the dimerization of BAD with BCL-XL. Thus, as previously shown for BAX, BAK, BCL-2, and BCL-XL, the BH3 domain of BAD is required for its dimerization with other BCL-2 family proteins. BAD was further analyzed for its ability to bind to various mutants of BCL-2 and BCL-XL that have lost the ability to bind BAX and BAK, some of which retain biological activity and some of which do not. Surprisingly, all of the mutated BCL-2 and BCL-XL proteins analyzed strongly interacted with human BAD. Our data thus indicate that mutations in BCL-2 and BCL-XL can differentially affect the heterodimeric binding of different death-promoting proteins and have implications concerning the relationship between heterodimerization and biological activity. |
