单位：[1]Key Laboratory of Molecular Biophysics of the Ministry of Education, National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.[2]Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China[3]Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA.[4]Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, China.华中科技大学同济医学院附属同济医院消化内科[5]Department of Pathogen Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China.[6]Wuhan Institute of Biotechnology, Wuhan 430070, China.
Although genome-wide association studies have identified the gene RNF186 encoding an E3 ubiquitin-protein ligase as conferring susceptibility to ulcerative colitis, the exact function of this protein remains unclear. In the present study, we demonstrate an important role for RNF186 in macroautophagy/autophagy activation in colonic epithelial cells and intestinal homeostasis. Mechanistically, RNF186 acts as an E3 ubiquitin-protein ligase for EPHB2 and regulates the ubiquitination of EPHB2. Upon stimulation by ligand EFNB1 (ephrin B1), EPHB2 is ubiquitinated by RNF186 at Lys892, and further recruits MAP1LC3B for autophagy. Compared to control mice, rnf186(-/-) and ephb2(-/-) mice have a more severe phenotype in the DSS-induced colitis model, which is due to a defect in autophagy in colon epithelial cells. More importantly, treatment with ephrin-B1-Fc recombinant protein effectively relieves DSS-induced mouse colitis, which suggests that ephrin-B1-Fc may be a potential therapy for human inflammatory bowel diseases.
基金：
This investigation was supported by the independent innovation grant from
Huazhong University of Science & Technology (grant 2017KFYXJJ163); and the grant from the
National Natural Science Foundation of China (grants 81871280); and the Junior Thousand Talents
Program of China (to C.H.W.).
第一作者单位：[1]Key Laboratory of Molecular Biophysics of the Ministry of Education, National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.
共同第一作者：
通讯作者：
通讯机构：[1]Key Laboratory of Molecular Biophysics of the Ministry of Education, National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.[6]Wuhan Institute of Biotechnology, Wuhan 430070, China.
推荐引用方式(GB/T 7714)：
Huazhi Zhang,Zhihui Cui,Du Cheng,et al.RNF186 regulates EFNB1 (ephrin B1)-EPHB2-induced autophagy in the colonic epithelial cells for the maintenance of intestinal homeostasis[J].AUTOPHAGY.2021,17(10):3030-3047.doi:10.1080/15548627.2020.1851496.
APA：
Huazhi Zhang,Zhihui Cui,Du Cheng,Yanyun Du,Xiaoli Guo...&Chenhui Wang.(2021).RNF186 regulates EFNB1 (ephrin B1)-EPHB2-induced autophagy in the colonic epithelial cells for the maintenance of intestinal homeostasis.AUTOPHAGY,17,(10)
MLA：
Huazhi Zhang,et al."RNF186 regulates EFNB1 (ephrin B1)-EPHB2-induced autophagy in the colonic epithelial cells for the maintenance of intestinal homeostasis".AUTOPHAGY 17..10(2021):3030-3047
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