The REGg-proteasome forms a regulatory circuit with IkBe and NFkB in experimental colitis
نویسندگان
چکیده
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 REGg, a proteasome activator, show significantly attenuated intestinal inflammation and colitis-associated cancer in dextran sodium sulfate model. Bone marrow transplantation experiments suggest that REGg’s function in non-haematopoietic cells primarily contributes to the phenotype. Elevated expression of REGg exacerbates local inflammation and promotes a reciprocal regulatory loop with NFkB involving ubiquitinindependent degradation of IkBe. Additional deletion of IkBe restored colitis phenotypes and inflammatory gene expression in REGg-deficient mice. In sum, this study identifies REGg-mediated control of IkBe as a molecular mechanism that contributes to NFkB activation and promotes bowel inflammation and associated tumour formation in response to chronic injury. DOI: 10.1038/ncomms10761 OPEN
منابع مشابه
The REGγ-proteasome forms a regulatory circuit with IκBɛ and NFκB in experimental colitis
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 REGγ, a proteasome activator, show significantly attenuated intestinal inflammation and colitis-associated cancer in dextran sodium sulfate model. Bone marrow transplantation experiments suggest that ...
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