| First Author | Bock FJ | Year | 2013 |
| Journal | Cell Death Differ | Volume | 20 |
| Issue | 4 | Pages | 546-57 |
| PubMed ID | 23238565 | Mgi Jnum | J:228266 |
| Mgi Id | MGI:5705728 | Doi | 10.1038/cdd.2012.152 |
| Citation | Bock FJ, et al. (2013) Loss of PIDD limits NF-kappaB activation and cytokine production but not cell survival or transformation after DNA damage. Cell Death Differ 20(4):546-57 |
| abstractText | Activation of NF-kappaB (nuclear factor of kappa light chain gene enhancer in B cells) in response to DNA damage is considered to contribute to repair of genetic lesions, increased cell survival and cytokine release. The molecular mechanisms orchestrating this cytoplasmic event involve core components of the nuclear DNA damage response machinery, including ATM-kinase (ataxia telangiectasia mutated kinase) and PARP-1 (poly (ADP-ribose) polymerase 1). The physiological consequences of defective NF-kappaB activation in this context, however, remain poorly investigated. Here we report on the role of the 'p53-induced protein with a death domain', PIDD, which appears rate limiting in this process, as is PARP-1. Despite impaired NF-kappaB activation, DNA damage did not increase cell death or reduce clonal survival of various cell types lacking PIDD, such as mouse embryonic fibroblasts or stem and progenitor cells of the hematopoietic system. Furthermore, lymphomagenesis induced by gamma-irradiation (IR) was unaffected by deficiency for PIDD or PARP-1, indicating that loss of DNA damage-triggered NF-kappaB signalling does not affect IR-driven tumorigenesis. However, loss of either gene compromised cytokine release after acute IR injury. Hence, we propose that NF-kappaB's most notable function after DNA damage in primary cells is related to the release of cytokines, thereby contributing to sterile inflammation. |
