| First Author | Mebratu YA | Year | 2008 |
| Journal | J Cell Biol | Volume | 183 |
| Issue | 3 | Pages | 429-39 |
| PubMed ID | 18981230 | Mgi Jnum | J:141068 |
| Mgi Id | MGI:3815339 | Doi | 10.1083/jcb.200801186 |
| Citation | Mebratu YA, et al. (2008) The BH3-only protein Bik/Blk/Nbk inhibits nuclear translocation of activated ERK1/2 to mediate IFNgamma-induced cell death. J Cell Biol 183(3):429-39 |
| abstractText | IFNgamma induces cell death in epithelial cells, but the mediator for this death pathway has not been identified. In this study, we find that expression of Bik/Blk/Nbk is increased in human airway epithelial cells (AECs [HAECs]) in response to IFNgamma. Expression of Bik but not mutant BikL61G induces and loss of Bik suppresses IFNgamma-induced cell death in HAECs. IFNgamma treatment and Bik expression increase cathepsin B and D messenger RNA levels and reduce levels of phospho-extracellular regulated kinase 1/2 (ERK1/2) in the nuclei of bik(+/+) compared with bik(-/-) murine AECs. Bik but not BikL61G interacts with and suppresses nuclear translocation of phospho-ERK1/2, and suppression of ERK1/2 activation inhibits IFNgamma- and Bik-induced cell death. Furthermore, after prolonged exposure to allergen, hyperplastic epithelial cells persist longer, and nuclear phospho-ERK is more prevalent in airways of IFNgamma(-/-) or bik(-/-) compared with wild-type mice. These results demonstrate that IFNgamma requires Bik to suppress nuclear localization of phospho-ERK1/2 to channel cell death in AECs. |
