| First Author | Oberkovitz G | Year | 2007 |
| Journal | Cell Death Differ | Volume | 14 |
| Issue | 9 | Pages | 1628-34 |
| PubMed ID | 17585339 | Mgi Jnum | J:141357 |
| Mgi Id | MGI:3818153 | Doi | 10.1038/sj.cdd.4402181 |
| Citation | Oberkovitz G, et al. (2007) Nucleocytoplasmic shuttling of BID is involved in regulating its activities in the DNA-damage response. Cell Death Differ 14(9):1628-34 |
| abstractText | The BH3-only BID protein acts as a sentinel to interconnect specific death signals to the core apoptotic pathway. Our previous data demonstrated that BID is important for both S-phase arrest and cell death following DNA damage, and that the cell cycle arrest function is regulated by its phosphorylation by the ATM kinase. We also showed that a portion of cellular BID localizes to the nucleus. Here, we demonstrate that etoposide and ionizing radiation induce the exit of BID from the nucleus and that leptomycin B, a specific inhibitor of the nuclear export receptor CRM1, prevents the nuclear exit of BID. BID carries a nuclear export signal (NES) consensus motif; however, it does not seem to be functional. To examine the importance of BID nuclear export, we targeted BID to the nucleus by fusing it to a strong nuclear localization signal (NLS). NLS-BID is phosphorylated in a similar time course as wild-type BID, but does not exit the nucleus following etoposide treatment. Importantly, introducing NLS-BID into BID(-/-) cells failed to restore S-phase arrest and cell death in response to etoposide. These results implicate BID as a nuclear protein and raise the possibility that nucleocytoplasmic shuttling of BID is involved in regulating its activities in the DNA-damage response. |
