Sam68/KHDRBS1-dependent NF-κB activation confers radioprotection to the colon epithelium in γ-irradiated mice

Kai Fu, Xin Sun, Eric M. Wier, Andrea Hodgson, Ryan P. Hobbs, Fengyi Wan

Research output: Contribution to journalArticle

Abstract

Previously we reported that Src-associated-substrate-during-mitosis-of-68kDa (Sam68/KHDRBS1) is pivotal for DNA damage-stimulated NF-κB transactivation of anti-apoptotic genes (Fu et al., 2016). Here we show that Sam68 is critical for genotoxic stress-induced NF-κB activation in the γ-irradiated colon and animal and that Sam68-dependent NF-κB activation provides radioprotection to colon epithelium in vivo. Sam68 deletion diminishes γ-irradiation-triggered PAR synthesis and NF-κB 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 γ-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-κB activation signaling in the colon tissue and whole animal and reveal the pathophysiological relevance of Sam68-dependent NF-κB activation in colonic cell survival and recovery from extrinsic DNA damage.

Original languageEnglish (US)
Article numbere21957
JournaleLife
Volume5
Issue numberDECEMBER2016
DOIs
StatePublished - Dec 20 2016

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Colon
Epithelium
Cape Verde
DNA Damage
Hand Injuries
Whole-Body Irradiation
Epithelial Cells
Porphobilinogen Synthase
Addison Disease
Mitosis
Knockout Mice
Transcriptional Activation
Cell Survival
Apoptosis
Genes
Library Catalogs
Cyclic AMP Receptor Protein
Cerebellar Ataxia
Blood Flow Velocity
Castration

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Fu, K., Sun, X., Wier, E. M., Hodgson, A., Hobbs, R. P., & Wan, F. (2016). Sam68/KHDRBS1-dependent NF-κB activation confers radioprotection to the colon epithelium in γ-irradiated mice. eLife, 5(DECEMBER2016), [e21957]. DOI: 10.7554/eLife.21957

Sam68/KHDRBS1-dependent NF-κB activation confers radioprotection to the colon epithelium in γ-irradiated mice. / Fu, Kai; Sun, Xin; Wier, Eric M.; Hodgson, Andrea; Hobbs, Ryan P.; Wan, Fengyi.

In: eLife, Vol. 5, No. DECEMBER2016, e21957, 20.12.2016.

Research output: Contribution to journalArticle

Fu, K, Sun, X, Wier, EM, Hodgson, A, Hobbs, RP & Wan, F 2016, 'Sam68/KHDRBS1-dependent NF-κB activation confers radioprotection to the colon epithelium in γ-irradiated mice' eLife, vol 5, no. DECEMBER2016, e21957. DOI: 10.7554/eLife.21957
Fu K, Sun X, Wier EM, Hodgson A, Hobbs RP, Wan F. Sam68/KHDRBS1-dependent NF-κB activation confers radioprotection to the colon epithelium in γ-irradiated mice. eLife. 2016 Dec 20;5(DECEMBER2016). e21957. Available from, DOI: 10.7554/eLife.21957

Fu, Kai; Sun, Xin; Wier, Eric M.; Hodgson, Andrea; Hobbs, Ryan P.; Wan, Fengyi / Sam68/KHDRBS1-dependent NF-κB activation confers radioprotection to the colon epithelium in γ-irradiated mice.

In: eLife, Vol. 5, No. DECEMBER2016, e21957, 20.12.2016.

Research output: Contribution to journalArticle

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