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- W2080563217 abstract "Tumor necrosis factor (TNF) is a therapeutic target in the treatment of inflammatory bowel disease; however, the exact role of TNF signaling in the colon epithelium remains unclear. We demonstrate that TNF activation of TNF receptor (R)1 stimulates both pro- and anti-apoptotic signaling pathways in the colon epithelium; however, TNFR1 protects against colon epithelial cell apoptosis following TNF exposure. To investigate anti-apoptotic signaling pathways downstream of TNFR1, we generated an intestinal epithelium-specific Raf knock-out mouse and identified Raf kinase as a key regulator of colon epithelial cell survival in response to TNF. Surprisingly, Raf promotes NF-kappaB p65 phosphorylation, independent of MEK signaling, to support cell survival. Taken together, these data demonstrate a novel pathway in which Raf promotes colon epithelial cell survival through NF-kappaB downstream of TNFR1 activation. Thus, further understanding of colon epithelial cell-specific TNFR signaling may result in the identification of new targets for inflammatory bowel disease treatment and define novel mediators of colitis-associated cancer." @default.
- W2080563217 created "2016-06-24" @default.
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- W2080563217 date "2008-10-01" @default.
- W2080563217 modified "2023-10-14" @default.
- W2080563217 title "TNFR1 Promotes Tumor Necrosis Factor-mediated Mouse Colon Epithelial Cell Survival through RAF Activation of NF-κB" @default.
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- W2080563217 doi "https://doi.org/10.1074/jbc.m801269200" @default.
- W2080563217 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2570867" @default.
- W2080563217 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/18713739" @default.
- W2080563217 hasPublicationYear "2008" @default.
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