| First Author | Fu K | Year | 2016 |
| Journal | Elife | Volume | 5 |
| PubMed ID | 27996939 | Mgi Jnum | J:269710 |
| Mgi Id | MGI:6205192 | Doi | 10.7554/eLife.21957 |
| Citation | Fu K, et al. (2016) Sam68/KHDRBS1-dependent NF-kappaB activation confers radioprotection to the colon epithelium in gamma-irradiated mice. Elife 5:e21957 |
| abstractText | Previously we reported that Src-associated-substrate-during-mitosis-of-68kDa (Sam68/KHDRBS1) is pivotal for DNA damage-stimulated NF-kappaB transactivation of anti-apoptotic genes (Fu et al., 2016). Here we show that Sam68 is critical for genotoxic stress-induced NF-kappaB activation in the gamma-irradiated colon and animal and that Sam68-dependent NF-kappaB activation provides radioprotection to colon epithelium in vivo. Sam68 deletion diminishes gamma-irradiation-triggered PAR synthesis and NF-kappaB activation in colon epithelial cells (CECs), thus hampering the expression of anti-apoptotic molecules in situ and facilitating CECs to undergo apoptosis in mice post whole-body gamma-irradiation (WBIR). Sam68 knockout mice suffer more severe damage in the colon and succumb more rapidly from acute radiotoxicity than the control mice following WBIR. Our results underscore the critical role of Sam68 in orchestrating genotoxic stress-initiated NF-kappaB activation signaling in the colon tissue and whole animal and reveal the pathophysiological relevance of Sam68-dependent NF-kappaB activation in colonic cell survival and recovery from extrinsic DNA damage. |
