Elevated O-GlcNAcylation promotes colonic inflammation and tumorigenesis by modulating NF-kappa B signaling
SCIE
SCOPUS
- Title
- Elevated O-GlcNAcylation promotes colonic inflammation and tumorigenesis by modulating NF-kappa B signaling
- Authors
- Yang, YR; Kim, DH; Seo, YK; Park, D; Jang, HJ; Choi, SY; Lee, YH; Lee, GH; Nakajima, K; Taniguchi, N; Kim, JM; Choi, EJ; Moon, HY; Kim, IS; Choi, JH; Lee, H; Ryu, SH; Cocco, L; Suh, PG
- Date Issued
- 2015-05-20
- Publisher
- IMPACT JOURNALS LLC
- Abstract
- O-GlcNAcylation is a reversible post-translational modification. O-GlcNAc addition and removal is catalyzed by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), respectively. More recent evidence indicates that regulation of O-GlcNAcylation is important for inflammatory diseases and tumorigenesis. In this study, we revealed that O-GlcNAcylation was increased in the colonic tissues of dextran sodium sulfate (DSS)-induced colitis and azoxymethane (AOM)/DSS-induced colitis-associated cancer (CAC) animal models. Moreover, the O-GlcNAcylation level was elevated in human CAC tissues compared with matched normal counterparts. To investigate the functional role of O-GlcNAcylation in colitis, we used OGA heterozygote mice, which have an increased level of O-GlcNAcylation. OGA(+/-) mice have higher susceptibility to DSS-induced colitis than OGA(+/+) mice. OGA(+/-) mice exhibited a higher incidence of colon tumors than OGA(+/+) mice. In molecular studies, elevated O-GlcNAc levels were shown to enhance the activation of NF-kappa B signaling through increasing the binding of RelA/p65 to its target promoters. We also found that Thr-322 and Thr352 in the p65-O-GlcNAcylation sites are critical for p65 promoter binding. These results suggest that the elevated O-GlcNAcylation level in colonic tissues contributes to the development of colitis and CAC by disrupting regulation of NF-kappa B-dependent transcriptional activity.
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/35472
- DOI
- 10.18632/oncotarget.3725
- ISSN
- 1949-2553
- Article Type
- Article
- Citation
- ONCOTARGET, vol. 6, no. 14, page. 12529 - 12542, 2015-05-20
- Files in This Item:
- There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.