| First Author | Barroso-González J | Year | 2016 |
| Journal | Cell Death Differ | Volume | 23 |
| Issue | 9 | Pages | 1448-57 |
| PubMed ID | 26943323 | Mgi Jnum | J:258907 |
| Mgi Id | MGI:6140889 | Doi | 10.1038/cdd.2016.23 |
| Citation | Barroso-Gonzalez J, et al. (2016) PACS-2 mediates the ATM and NF-kappaB-dependent induction of anti-apoptotic Bcl-xL in response to DNA damage. Cell Death Differ 23(9):1448-57 |
| abstractText | Nuclear factor kappa B (NF-kappaB) promotes cell survival in response to genotoxic stress by inducing the expression of anti-apoptotic proteins including Bcl-xL, which protects mitochondria from stress-induced mitochondrial outer membrane permeabilization (MOMP). Here we show that the multifunctional sorting protein Pacs-2 (phosphofurin acidic cluster sorting protein-2) is required for Bcl-xL induction following DNA damage in primary mouse thymocytes. Consequently, in response to DNA damage, Pacs-2(-/-) thymocytes exhibit a blunted induction of Bcl-xL, increased MOMP and accelerated apoptosis. Biochemical studies show that cytoplasmic PACS-2 promotes this DNA damage-induced anti-apoptotic pathway by interacting with ataxia telangiectasia mutated (ATM) to drive NF-kappaB activation and induction of Bcl-xL. However, Pacs-2 was not required for tumor necrosis factor-alpha-induced NF-kappaB activation, suggesting a role for PACS-2 selectively in NF-kappaB activation in response to DNA damage. These findings identify PACS-2 as an in vivo mediator of the ATM and NF-kappaB-dependent induction of Bcl-xL that promotes cell survival in response to DNA damage. |
