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Regulation of antiviral innate immunity by deubiquitinase CYLD

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Cellular & Molecular Immunology 2011年第6期8卷 502-504页

作者： Minying Zhang Andrew J Lee Xuefeng Wu Shao-Cong Sun Department of Immunology The University of Texas MD Anderson Cancer CenterHoustonTXUSA Department of Melanoma Medical Oncology The University of Texas MD Anderson Cancer CenterHoustonTXUSA Laboratory of Gene Regulation and Signal Transduction Department of PharmacologySchool of MedicineUniversity of California at San DiegoLa JollaCAUSA

An antiviral innate immune response involves induction of type I interferons(IFNs)and their subsequent autocrine and paracrine actions,but the underlying regulatory mechanisms are incompletely understood.Here we report that CYLD,a deubiquitinase that specifically digests lysine 63-linked ubiquitin chains,is required for antiviral host defense.Loss of CYLD renders mice considerably more susceptible to infection by vesicular stomatitis virus(VSV).Consistently,CYLD-deficient dendritic cells are more sensitive to VSV infection.This functional defect was not due to lack of type I IFN production but rather because of attenuated IFN receptor signaling.In the absence of CYLD,IFN-b is ineffective in the induction of antiviral genes and protection of cells from viral infection.These findings establish CYLD as a novel regulator of antiviral innate immunity and suggest a role for CYLD in regulating IFN receptor signaling.

关键词： antiviral innate immunity CYLD deubiquitinase interferon VSV

OTUD5 promotes innate antiviral and antitumor immunity through deubiquitinating and stabilizing STING

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Cellular & Molecular Immunology 2021年第8期18卷 1945-1955页

作者： Yunyun Guo Fei Jiang Lingli Kong Haifeng Wu Honghai Zhang Xiaorong Chen Jian Zhao Baoshan Cai Yanqi Li Chunhong Ma Fan Yi Lei Zhang Bingyu Liu Yi Zheng Lingqiang Zhang Chengjiang Gao Key Laboratory of Infection and immunity of Shandong Province&Department of Immunology School of Biomedical SciencesShandong University250012JinanShandongPeople’s Republic of China Department of Pharmacology School of Biomedical SciencesShandong University250012JinanShandongPeople’s Republic of China State Key Laboratory of Proteomics Beijing Proteome Research CenterNational Center for Protein Sciences(Beijing)Beijing Institute of Lifeomics100850BeijingPeople’s Republic of China

Stimulator of interferon genes(STING)is an adaptor protein that is critical for effective innate antiviral and antitumor immunity.The activity of STING is heavily regulated by protein ubiquitination,which is fine-tuned by both E3 ubiquitin ligases and deubiquitinases.Here,we report that the deubiquitinase OTUD5 interacts with STING,cleaves its K48-linked polyubiquitin chains,and promotes its stability.Consistently,knockout of OTUD5 resulted in faster turnover of STING and subsequently impaired type I IFN signaling following cytosolic DNA stimulation.More importantly,Lyz2-Cre Otud5^(fl/Y) mice and CD11-Cre Otud5^(fl/Y) mice showed more susceptibility to herpes simplex virus type 1(HSV-1)infection and faster development of melanomas than their corresponding control littermates,indicating that OTUD5 is indispensable for STING-mediated antiviral and antitumor immunity.Our data suggest that OTUD5 is a novel checkpoint in the cGAS-STING cytosolic DNA sensing pathway.

关键词： antiviral innate immunity antitumor immunity STING deubiquitination OTUD5

N4 DNA recognition by STAT6： structural and functional implications

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Protein & Cell 2017年第4期8卷 240-241页

作者： Xiang Zhou Zhengfan Jiang Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education State Key Laboratory of Protein and Plant Gene Research School of Life Sciences Peking University Beijing 100871 China Peking-Tsinghua Center for Life Sciences Beijing 100871 China

On Nov. 1st 2016, a research paper titled Structural basis for DNA recognition by STAT6 was published online on PNAS （Li et al., 2016）, which revealed for the first time the mech- anism of signal transducer and activator of transcription 6 （STAT6） recognition by DNA with N4 site. The authors are from the Institute of Biophysics, Chinese Academy of Sciences （CAS）.

关键词： Stat Protein Host innate Immune Response antiviral innate immunity Stat Family Protein

ZDHHC18 modulates cGAS-mediated innate immunity by palmitoylating and inhibiting its enzyme activity

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ZDHHC18 modulates cGAS-mediated innate immunity by palmitoyl...

Ubiquitin-specific protease 4(USP4) positively regulates RIG-Ⅰsignaling through deubiquitination and stabilization of RIG-Ⅰ

第十一届全国化学生物学学术会议

作者： Chengrui Shi Xikang Yang Ying Zhang Hang Ying School of Pharmacy Tsinghua University

The cyclic GMP-AMP synthase(cGAS) is a sensor of cytosolic viral DNA and upon DNA sensing,catalyzes the formation of the second messenger cyclic GMP-AMP(cGAMP) that binds to STING and activates the immune response.Protein palmitoylation,the addition of palmitate to a Cys residue of protein,is a post-translation modification which often influences,protein trafficking,protein stability and protein aggregation.Activation of cGAS can be modulated by several protein posttranslational modifications.However,whether activation of cGAS can be regulated by palmitoylation remains poorly understood.In this study,we indentified that cGAS is a palmitoylated protein mainly catalyzed by DHHC18 acetyltransferase.Overexpression of ZDHHC18 inhibits c GAS-mediated immune response,whereas knockdown of PCBP2 exerted the opposite effect.ZDHHC18 mediated c GAS palmitoylation attenuated the production of cGAMP in human macrophages which shows a "fine tuning" of antiviral innate immunity.

关键词： cGAS Palmitoylation antiviral innate immunity

来源： cnki会议评论

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Ubiquitin-specific protease 4(USP4) positively regulates RIG...

The long and short isoforms of tree shrew MITA play distinct roles in DNA virus and RNA virus infections

细胞—生命的基础——中国细胞生物学学会2013年全国学...

作者： Lijuan Wang Wei Zhao Chengjiang Gao Department of Immunology Shandong University the School of Medicine

Retinoic acid-inducible gene I(RIG-I) is a major cytosolic RNA sensor to detect RNA virus and initiate the antiviral innate immune response.Protein ubiquitination has been shown to play an essential role in the regulation of RIG-I activation.Ubiquitin E3 ligase TRIM25 and Riplet conjugate K63-linked polyubiquitin chains to RIG-I,leading to the activation of RIG-I.While,other E3 ligase such as RNF125 and c-Cbl could conjugate K48-linked polyubiquitin chains to RIG-I,leading to the

关键词： antiviral innate immunity RIG-I USP4 deubiquitination

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The long and short isoforms of tree shrew MITA play distinct...