Please wait a minute...
浙江大学学报（医学版）
J Zhejiang Univ (Med Sci)  2018, Vol. 47 Issue (1): 82-88    DOI: 10.3785/j.issn.1008-9292.2018.02.12
    
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
Download: HTML( 6 )   PDF(1074KB)
Export: BibTeX | EndNote (RIS)      

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     
Received: 06 January 2018      Published: 12 June 2018
CLC:  R392  
Corresponding Authors: CHEN Weilin     E-mail: lingjing@zju.edu.cn;cwl@zju.edu.cn
Service
E-mail this article
Add to my bookshelf
Add to citation manager
E-mail Alert
RSS
Articles by authors
LING Jing
LI Hongrui
CHEN Weilin
Cite this article:

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.

URL:

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


蛋白泛素化修饰调控炎性肠疾病发生和发展的研究进展

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 
Fig 1 RNF183, RNF20, Itch and A20 regulate pathogenesis of inflammatory bowel disease
[1]   MALOY K J , POWRIE F . Intestinal homeostasis and its breakdown in inflammatory bowel disease[J]. Nature, 2011, 474 (7351): 298- 306
doi: 10.1038/nature10208
[2]   YU Q , ZHANG S , CHAO K et al. E3 Ubiquitin ligase RNF183 is a novel regulator in inflammatory bowel disease[J]. J Crohns Colitis, 2016, 10 (6): 713- 725
doi: 10.1093/ecco-jcc/jjw023
[3]   GEREMIA A , BIANCHERI P , ALLAN P et al. Innate and adaptive immunity in inflammatory bowel disease[J]. Autoimmun Rev, 2014, 13 (1): 3- 10
doi: 10.1016/j.autrev.2013.06.004
[4]   ROY U , EJC G , ILJAZOVIC A et al. Distinct microbial communities trigger colitis development upon intestinal barrier damage via innate or adaptive immune cells[J]. Cell Rep, 2017, 21 (4): 994- 1008
doi: 10.1016/j.celrep.2017.09.097
[5]   NG S C , SHI H Y , HAMIDI N et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century:a systematic review of population-based studies[J]. Lancet, 2018, 390 (10114): 2769- 2778
[6]   CHEN J , CHEN Z J . Regulation of NF-kappaB by ubiquitination[J]. Cur Opin Immunol, 2013, 25 (1): 4- 12
doi: 10.1016/j.coi.2012.12.005
[7]   SWATEK K N , KOMANDER D . Ubiquitin modifications[J]. Cell Res, 2016, 26 (4): 399- 422
doi: 10.1038/cr.2016.39
[8]   SCHULMAN B A , HARPER J W . Ubiquitin-like protein activation by E1 enzymes:the apex for downstream signalling pathways[J]. Nat Rev Mol Cell Biol, 2009, 10 (5): 319- 331
[9]   YE Y , RAPE M . Building ubiquitin chains:E2 enzymes at work[J]. Nat Rev Mol Cell Biol, 2009, 10 (11): 755- 764
doi: 10.1038/nrm2780
[10]   DESHAIES R J , JOAZEIRO C A . RING domain E3 ubiquitin ligases[J]. Annu Rev Biochem, 2009, 78 399- 434
doi: 10.1146/annurev.biochem.78.101807.093809
[11]   SONG H , LIU B , HUAI W et al. The E3 ubiquitin ligase TRIM31 attenuates NLRP3 inflammasome activation by promoting proteasomal degradation of NLRP3[J]. Nat Commun, 2016, 7 13727
doi: 10.1038/ncomms13727
[12]   ZAKI M H , BOYD K L , VOGEL P et al. The NLRP3 inflammasome protects against loss of epithelial integrity and mortality during experimental colitis[J]. Immunity, 2010, 32 (3): 379- 391
doi: 10.1016/j.immuni.2010.03.003
[13]   SHU X S , ZHAO Y , ZHONG L et al. The epigenetic modifier PBRM1 restricts the basal activity of the innate immune system by repressing retinoic acid-inducible gene-l-like receptor signalling and is a potential prognostic biomarker for colon cancer[J]. J Pathol, 2018, 244 (1): 36- 48
doi: 10.1002/path.4986
[14]   CAO Z , CONWAY K L , HEATH R J et al. Ubiquitin ligase TRIM62 regulates CARD9-mediated anti-fungal immunity and intestinal inflammation[J]. Immunity, 2015, 43 (4): 715- 726
doi: 10.1016/j.immuni.2015.10.005
[15]   YANG S , WANG B , HUMPHRIES F et al. Pellino3 ubiquitinates RIP2 and mediates Nod2-induced signaling and protective effects in colitis[J]. Nat Immunol, 2013, 14 (9): 927- 936
doi: 10.1038/ni.2669
[16]   NAKAMURA N . The role of the transmembrane RING finger proteins in cellular and organelle function[J]. Membranes(Basel), 2011, 1 (4): 354- 393
[17]   HEUZé M L , LAMSOUL I , MOOG-LUTZ C et al. Ubiquitin-mediated proteasomal degradation in normal and malignant hematopoiesis[J]. Blood Cells Mol Dis, 2008, 40 (2): 200- 210
doi: 10.1016/j.bcmd.2007.07.011
[18]   DUTTA J , FAN Y , GUPTA N et al. Current insights into the regulation of programmed cell death by NF-kappaB[J]. Oncogene, 2006, 25 (51): 6800- 6816
doi: 10.1038/sj.onc.1209938
[19]   GENG R , TAN X , WU J et al. RNF183 promotes proliferation and metastasis of colorectal cancer cells via activation of NF-kappaB-IL-8 axis[J]. Cell Death Dis, 2017, 8 (8): e2994
doi: 10.1038/cddis.2017.400
[20]   GENG R , TAN X , ZUO Z et al. Synthetic lethal short hairpin RNA screening reveals that ring finger protein 183 confers resistance to trametinib in colorectal cancer cells[J]. Chin J Cancer, 2017, 36 (1): 63
doi: 10.1186/s40880-017-0228-1
[21]   CAMPOS E I , REINBERG D . Histones:annotating chromatin[J]. Annu Rev Genet, 2009, 43 559- 599
doi: 10.1146/annurev.genet.032608.103928
[22]   TARCIC O , PATERAS I S , COOKS T et al. RNF20 links histone H2B ubiquitylation with inflammation and inflammation-associated cancer[J]. Cell Rep, 2016, 14 (6): 1462- 1476
doi: 10.1016/j.celrep.2016.01.020
[23]   MINSKY N , SHEMA E , FIELD Y et al. Monoubiquitinated H2B is associated with the transcribed region of highly expressed genes in human cells[J]. Nat Cell Biol, 2008, 10 (4): 483- 488
doi: 10.1038/ncb1712
[24]   PAVRI R , ZHU B , LI G et al. Histone H2B monoubiquitination functions cooperatively with FACT to regulate elongation by RNA polymerase Ⅱ[J]. Cell, 2006, 125 (4): 703- 717
doi: 10.1016/j.cell.2006.04.029
[25]   KATOH H , WANG D , DAIKOKU T et al. CXCR2-expressing myeloid-derived suppressor cells are essential to promote colitis-associated tumorigenesis[J]. Cancer Cell, 2013, 24 (5): 631- 644
doi: 10.1016/j.ccr.2013.10.009
[26]   WU P , WU D , NI C et al. γδT17 cells promote the accumulation and expansion of myeloid-derived suppressor cells in human colorectal cancer[J]. Immunity, 2014, 40 (5): 785- 800
doi: 10.1016/j.immuni.2014.03.013
[27]   GRIVENNIKOV S I , WANG K , MUCIDA D et al. Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth[J]. Nature, 2012, 491 (7423): 254- 258
doi: 10.1038/nature11465
[28]   DONG C . Th17 cells in development:an updated view of their molecular identity and genetic programming[J]. Nat Rev Immunol, 2008, 8 (5): 337- 348
doi: 10.1038/nri2295
[29]   ZHANG F , MENG G , STROBER W . Interactions among the transcription factors Runx1, RORγ and Foxp3 regulate the differentiation of interleukin 17-producing T cells[J]. Nat Immunol, 2008, 9 (11): 1297- 1306
doi: 10.1038/ni.1663
[30]   KATHANIA M , KHARE P , ZENG M et al. Itch inhibits IL-17-mediated colon inflammation and tumorigenesis by ROR-gammat ubiquitination[J]. Nat Immunol, 2016, 17 (8): 997- 1004
doi: 10.1038/ni.3488
[31]   TAO M , SCACHERI P C , MARINIS J M et al. ITCH directly K63-ubiquitinates the NOD2 binding protein, RIP2, to influence inflammatory signaling pathways[J]. Curr Biol, 2009, 19 (15): 1255- 1263
doi: 10.1016/j.cub.2009.06.038
[32]   LATELLA G , DI G J , FLATI V et al. Mechanisms of initiation and progression of intestinal fibrosis in IBD[J]. Scand J Gastroenterol, 2015, 50 (1): 53- 65
doi: 10.3109/00365521.2014.968863
[33]   PAUL J , SINGH A K , KATHANIA M et al. IL-17-driven intestinal fibrosis is inhibited by Itch-mediated ubiquitination of HIC-5[J]. Mucosal Immunol, 2018, 11 (2): 427- 436
doi: 10.1038/mi.2017.53
[34]   VEREECKE L , BEYAERT R , VAN LOO G . The ubiquitin-editing enzyme A20(TNFAIP3) is a central regulator of immunopathology[J]. Trends Immunol, 2009, 30 (8): 383- 391
doi: 10.1016/j.it.2009.05.007
[35]   HOLLERAN G , LOPETUSO L , PETITO V et al. The innate and adaptive immune system as targets for biologic therapies in inflammatory bowel disease[J]. Int J Mol Sci, 2017, 18 (10): 2020
doi: 10.3390/ijms18102020
[36]   YE D , MA I , MA T Y . Molecular mechanism of tumor necrosis factor-alpha modulation of intestinal epithelial tight junction barrier[J]. Am J Physiol Gastrointest Liver Physiol, 2006, 290 (3): G496- G504
doi: 10.1152/ajpgi.00318.2005
[37]   BAO C H , WU L Y , SHI Y et al. Moxibustion down-regulates colonic epithelial cell apoptosis and repairs tight junctions in rats with Crohn's disease[J]. World J Gastroenterol, 2011, 17 (45): 4960- 4970
doi: 10.3748/wjg.v17.i45.4960
[38]   EVANS P C , OVAA H , HAMON M et al. Zinc-finger protein A20, a regulator of inflammation and cell survival, has de-ubiquitinating activity[J]. Biochem J, 2004, 378 (Pt 3): 727- 734
[39]   KOLODZIEJ L E , LODOLCE J P , CHANG J E et al. TNFAIP3 maintains intestinal barrier function and supports epithelial cell tight junctions[J]. PLoS One, 2011, 6 (10): e26352
doi: 10.1371/journal.pone.0026352
[1] JIANG Xiyi, LI Lu, TANG Huijuan, CHEN Tianhui. Multiple risk factors prediction models for high risk population of colorectal cancer[J]. J Zhejiang Univ (Med Sci), 2018, 47(2): 194-200.
[2] HE Yuxian, ZHENG Liangrong. Effect of spinal cord stimulation on myocardial ischemia/infarction[J]. J Zhejiang Univ (Med Sci), 2018, 47(2): 201-206.
[3] LYU Dandan, YING Kejing. Regulatory role of autophagy in development of pulmonary artery hypertension[J]. J Zhejiang Univ (Med Sci), 2018, 47(2): 207-212.
[4] DING Jingjing,LU Yunbi. Research progress on receptor interacting proteins in inflammation[J]. J Zhejiang Univ (Med Sci), 2018, 47(1): 89-96.
[5] TANG Huijuan,JIANG Xiyi,LOU Jianlin,CHEN Tianhui. Methodology for survival assessment of cancer patients using population-based cancer registration data[J]. J Zhejiang Univ (Med Sci), 2018, 47(1): 104-109.
[6] ZHANG Yuchuan,CHEN Wei. Regulatory effect of Vav1 on T cells and its relation to clinical diseases[J]. J Zhejiang Univ (Med Sci), 2018, 47(1): 75-81.
[7] WANG Jiajing,GU Haiying. Research progress on genotyping of Helicobacter pylori[J]. J Zhejiang Univ (Med Sci), 2018, 47(1): 97-103.
[8] FENG Mengyu,ZHANG Taiping,ZHAO Yupei. Present situation and prospect of enhanced recovery after surgery in pancreatic surgery[J]. J Zhejiang Univ (Med Sci), 2017, 46(6): 666-674.
[9] XU Jingjing, TAN Yanbin, ZHANG Minming. Medical imaging in tumor precision medicine: opportunities and challenges[J]. J Zhejiang Univ (Med Sci), 2017, 46(5): 455-461.
[10] PAN Jingying, HE Mengye, KE Wei, HU Menglin, WANG Meifang, SHEN Peng. Advances on correlation of PET-CT findings with breast cancer molecular subtypes, treatment response and prognosis[J]. J Zhejiang Univ (Med Sci), 2017, 46(5): 473-480.
[11] ZHANG Siying, CHEN Feng. Research progress of CT/MRI parametric response map in precision evaluation of therapeutic response of cancer patients[J]. J Zhejiang Univ (Med Sci), 2017, 46(5): 468-472.
[12] PAN Yao, CHEN Jieyu, YU Risheng. Accurate imaging diagnosis and evaluation of pancreatic cancer[J]. J Zhejiang Univ (Med Sci), 2017, 46(5): 462-467.
[13] WANG Mengyan, ZHU Biao. Research progress on genes mutations related to sulfa drug resistance in Pneumocystis jirovecii[J]. J Zhejiang Univ (Med Sci), 2017, 46(5): 563-569.
[14] LI Yandie, LU Meiping. Progress on the study of NLRP3 inflammasome in autoinflammatory diseases of children[J]. J Zhejiang Univ (Med Sci), 2017, 46(4): 449-453.
[15] WANG Liya, QIAN Yeqing, JIN Fan. Research progress on the safety of offsprings conceived by assisted reproductive technology[J]. J Zhejiang Univ (Med Sci), 2017, 46(3): 279-284.