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浙江大学学报（医学版）
浙江大学学报（医学版）  2018, Vol. 47 Issue (1): 82-88    DOI: 10.3785/j.issn.1008-9292.2018.02.12
综述     
蛋白泛素化修饰调控炎性肠疾病发生和发展的研究进展
凌静1(),李红蕊1,陈玮琳1,2,*()
1. 浙江大学医学院免疫学研究所, 浙江 杭州 310058
2. 深圳大学医学部免疫学系, 广东 深圳 518060
Protein ubiquitination on the regulation of inflammatory bowel disease
LING Jing1(),LI Hongrui1,CHEN Weilin1,2,*()
1. Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China
2. Department of Immunology, Shenzhen University School of Medicine, Shenzhen 518060, China
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摘要：

炎性肠疾病是一种慢性胃肠道功能紊乱的炎症性疾病。泛素化是一类重要的蛋白质翻译后修饰方式。近年来关于泛素化-去泛素化系统在炎性肠疾病发生和发展中的作用已成为研究热点。目前蛋白泛素化修饰调控炎性肠疾病过程所需的E3泛素连接酶中，分子生物学研究较为清楚的有环指蛋白183（RNF183）、环指蛋白20（RNF20）、Itch和锌指蛋白A20。其中RNF183可靶向核因子κB抑制蛋白α（IκBα）泛素化降解促进NF-κB活化；RNF20促进组蛋白H2B单泛素化从而下调相关炎症因子的转录；Itch促进维甲酸核孤儿受体γt泛素化降解抑制IL-17介导的肠炎；A20以其特有的泛素化和去泛素化双重活性影响炎性肠疾病的发展。本文综述了以上分子在炎性肠疾病发生、发展和转归中的作用及调控机制。
关键词： 泛素化;  泛素蛋白连接酶类;  炎性肠疾病;  综述    
Abstract:

Inflammatory bowel disease refers to chronic inflammatory disorders that affect the gastrointestinal tract. Ubiquitination is an important protein post-translational modification. In recent years, the research of ubiquitination-deubiquitination system in the development of inflammatory bowel disease has become a hot spot. Up to now, the E3 ubiquitin ligases such as ring finger protein 183 (RNF183), RNF20, Itch and A20 were well studied in inflammatory bowel disease. RNF183 promotes the activation of the NF-κB pathway by increasing the ubiquitination and degradation of IκBα; RNF20 drives histone H2B monoubiquitylation, downregulates a panel of inflammation-associated genes; Itch inhibits IL-17-mediated colon inflammation by retinoid acid related orphan receptor γt ubiquitination; A20 has ubiquitinating-deubiquitinating activity to regulates colon inflammation. This article reviews the role and regulatory mechanism of RNF183, RNF20, Itch and A20 in the pathogenesis of inflammatory bowel disease.
Key words: Ubiquitination    Ubiquitin-protein ligases    Inflammatory bowel diseases    Review
收稿日期: 2018-01-06 出版日期: 2018-06-12
CLC:  R392  
基金资助: 浙江省自然科学基金(LZ17H100001);国家自然科学基金(31670914)
通讯作者: 陈玮琳     E-mail: lingjing@zju.edu.cn;cwl@zju.edu.cn
作者简介: 凌静(1993-), 女, 硕士研究生, 主要从事感染免疫学研究; E-mail:lingjing@zju.edu.cn; https://orcid.org/0000-0002-9163-2542
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凌静
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引用本文:

凌静,李红蕊,陈玮琳. 蛋白泛素化修饰调控炎性肠疾病发生和发展的研究进展[J]. 浙江大学学报（医学版）, 2018, 47(1): 82-88.

LING Jing,LI Hongrui,CHEN Weilin. Protein ubiquitination on the regulation of inflammatory bowel disease. J Zhejiang Univ (Med Sci), 2018, 47(1): 82-88.

链接本文:

http://www.zjujournals.com/med/CN/10.3785/j.issn.1008-9292.2018.02.12    或    http://www.zjujournals.com/med/CN/Y2018/V47/I1/82

图 1  RNF183、RNF20、Itch和A20对炎性肠疾病发生、发展的调控机制
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