The membrane-associated E3 ubiquitin ligase MARCH3 downregulates the IL-6 receptor and suppresses colitis-associated carcinogenesis
作者机构：Department of Infectious DiseasesZhongnan Hospital of Wuhan UniversityMedical Research InstituteFrontier Science Center for Immunology and MetabolismResearch Unit of Innate Immune and Inflammatory DiseasesChinese Academy of Medical SciencesWuhan UniversityWuhan430071China Wuxi Cancer InstituteAffiliated Hospital of Jiangnan UniversityWuxi214062JiangsuChina
出 版 物：《Cellular & Molecular Immunology》 (中国免疫学杂志（英文版）)
年 卷 期：2021年第18卷第12期
页 面：2648-2659页
核心收录：
学科分类：1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100214[医学-肿瘤学] 10[医学]
基 金：This work was supported by grants from the National Key R&D Program of China(2017YFA0505800) the National Natural Science Foundation of China(31630045,31830024,31900556,and 32070775) the CAMS Innovation Fund for Medical Sciences(2019-I2M-5-071) the National Postdoctoral Program for Innovative Talents(BX20190255) the China Postdoctoral Science Foundation(2019M662706)
主 题：MARCH3 IL-6 IL-6Ra colitis-associated carcinogenesis polyubiquitination
摘 要：The IL-6-STAT3 axis is critically involved in inflammation-associated carcinogenesis(IAC).How this axis is regulated to modulate IAC remains ***,we show that the plasma membrane-associated E3 ubiquitin ligase MARCH3 negatively regulates STAT3 activation triggered by IL-6,as well as another IL-6 subfamily member,Oncostatin M(OSM).MARCH3 is associated with the IL-6 receptorα-chain(IL-6Rα)and its coreceptor *** experiments indicated that MARCH3 mediates the polyubiquitination of IL-6Rαat K401 and gp130 at K849 following IL-6 stimulation,leading to their translocation to and degradation in ***3 deficiency increases IL-6-and OSM-triggered activation of STAT3 and induction of downstream effector genes in various cell ***3 deficiency enhances dextran sulfate sodium(DSS)-induced STAT3 activation,increases the expression of inflammatory cytokines,and exacerbates colitis,as well as azoxymethane(AOM)/DSS-induced colitis-associated cancer in *** addition,MARCH3 is downregulated in human colorectal cancer tissues and associated with poor survival across different cancer *** findings suggest that MARCH3 is a pivotal negative regulator of IL-6-induced STAT3 activation,inflammation,and inflammation-associated carcinogenesis.
维普期刊数据库