| First Author | Xu J | Year | 2016 |
| Journal | Nat Commun | Volume | 7 |
| Pages | 10761 | PubMed ID | 26899380 |
| Mgi Jnum | J:234733 | Mgi Id | MGI:5790755 |
| Doi | 10.1038/ncomms10761 | Citation | Xu J, et al. (2016) The REGgamma-proteasome forms a regulatory circuit with IkappaBvarepsilon and NFkappaB in experimental colitis. Nat Commun 7:10761 |
| abstractText | Increasing incidence of inflammatory bowel disorders demands a better understanding of the molecular mechanisms underlying its multifactorial aetiology. Here we demonstrate that mice deficient for REGgamma, a proteasome activator, show significantly attenuated intestinal inflammation and colitis-associated cancer in dextran sodium sulfate model. Bone marrow transplantation experiments suggest that REGgamma's function in non-haematopoietic cells primarily contributes to the phenotype. Elevated expression of REGgamma exacerbates local inflammation and promotes a reciprocal regulatory loop with NFkappaB involving ubiquitin-independent degradation of IkappaBvarepsilon. Additional deletion of IkappaBvarepsilon restored colitis phenotypes and inflammatory gene expression in REGgamma-deficient mice. In sum, this study identifies REGgamma-mediated control of IkappaBvarepsilon as a molecular mechanism that contributes to NFkappaB activation and promotes bowel inflammation and associated tumour formation in response to chronic injury. |
