| First Author | De Zio D | Year | 2011 |
| Journal | Cell Death Differ | Volume | 18 |
| Issue | 3 | Pages | 516-27 |
| PubMed ID | 20966962 | Mgi Jnum | J:186325 |
| Mgi Id | MGI:5432047 | Doi | 10.1038/cdd.2010.125 |
| Citation | De Zio D, et al. (2011) The DNA repair complex Ku70/86 modulates Apaf1 expression upon DNA damage. Cell Death Differ 18(3):516-27 |
| abstractText | Apaf1 is a key regulator of the mitochondrial intrinsic pathway of apoptosis, as it activates executioner caspases by forming the apoptotic machinery apoptosome. Its genetic regulation and its post-translational modification are crucial under the various conditions where apoptosis occurs. Here we describe Ku70/86, a mediator of non-homologous end-joining pathway of DNA repair, as a novel regulator of Apaf1 transcription. Through analysing different Apaf1 promoter mutants, we identified an element repressing the Apaf1 promoter. We demonstrated that Ku70/86 is a nuclear factor able to bind this repressing element and downregulating Apaf1 transcription. We also found that Ku70/86 interaction with Apaf1 promoter is dynamically modulated upon DNA damage. The effect of this binding is a downregulation of Apaf1 expression immediately following the damage to DNA; conversely, we observed Apaf1 upregulation and apoptosis activation when Ku70/86 unleashes the Apaf1-repressing element. Therefore, besides regulating DNA repair, our results suggest that Ku70/86 binds to the Apaf1 promoter and represses its activity. This may help to inhibit the apoptosome pathway of cell death and contribute to regulate cell survival. |
