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Legionella pneumophila-mediated host posttranslational modifications

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Journal of Molecular Cell Biology 2023年第5期15卷 7-20页

作者： Yi Yang Ligang Mei Jing Chen Xiaorong Chen Zhuolin Wang Lu Liu Aimin Yang School of Life Sciences Chongqing UniversityChongqing 401331China

Legionella pneumophila is a Gram-negative bacterium ubiquitously present in freshwater environments and causes a serious type of pneumonia called Legionnaires’*** infections,*** releases over 300 effector proteins into host cells through an Icm/Dot type IV secretion system to manipulate the host defense system for survival within the ***,certain effector proteins mediate posttranslational modifications(PTMs),serving as useful approaches exploited by *** to modify host *** effectors catalyze the addition of host protein PTMs,while others mediate the removal of PTMs from host *** this review,we summarize *** effector-mediated PTMs of host proteins,including phosphorylation,ubiquitination,glycosylation,AMPylation,phosphocholination,methylation,and ADP-ribosylation,as well as dephosphorylation,deubiquitination,deAMPylation,deADP-ribosylation,dephosphocholination,and *** describe their molecular mechanisms and biological functions in the regulation of bacterial growth and Legionella-containing vacuole biosynthesis and in the disruption of host immune and defense machinery.

关键词： Legionella pneumophila bacterial effector posttranslational modification host-pathogen interaction Legionellacontaining vacuole pathogenesis host defense system

LncRNA-mediated posttranslational modifications and reprogramming of energy metabolism in cancer

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Cancer Communications 2021年第2期41卷 109-120页

作者： Yue-Tao Tan Jin-Fei Lin Ting Li Jia-Jun Li Rui-Hua Xu Huai-Qiang Ju Department of Medical Oncology Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouGuangdong 510060P.R.China Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer Chinese Academy of Medical SciencesGuangzhouGuangdong 510060P.R.China

Altered metabolism is a hallmark of cancer,and the reprogramming of energy metabolism has historically been considered a general phenomenon of *** is well recognized that long noncoding RNAs(lncRNAs)regulate energy metabolism in ***,lncRNA-mediated posttranslational modifications and metabolic reprogramming are unclear at *** this review,we summarized the current understanding of the interactions between the alterations in cancer-associated energy metabolism and the lncRNA-mediated posttranslational modifications of metabolic enzymes,transcription factors,and other proteins involved in metabolic *** addition,we discuss the mechanisms through which these interactions contribute to tumor initiation and progression,and the key roles and clinical significance of functional *** believe that an in-depth understanding of lncRNA-mediated cancer metabolic reprogramming can help to identify cellular vulnerabilities that can be exploited for cancer diagnosis and therapy.

关键词： cancer metabolism enzyme long noncoding RNA metabolic reprogramming posttranslational modification

Global characterization of modifications to the charge isomers of IgG antibody

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Journal of Pharmaceutical Analysis 2022年第1期12卷 156-163页

作者： Xinling Cui Wei Mi Zhishang Hu Xiaoyu Li Bo Meng Xinyuan Zhao Xiaohong Qian Tao Zhu Wantao Ying State Key Laboratory of Proteomics Beijing Proteome Research CenterNational Center for Protein Sciences(Beijing)Beijing Institute of LifeomicsBeijingChina National Institute of Metrology Center for Advanced Measurement ScienceBeijingChina National Institute of Metrology Chemical Metrology&Analytical Science DivisionBeijingChina CanSino Bio Corporation Tianjin Key Laboratory of Recombinant Bacterial Recombination and Bacterial Vaccines TianjinChina

posttranslational modifications of antibody products affect their stability,charge distribution,and drug activity and are thus a critical quality *** comprehensive mapping of antibody modifications and different charge isomers(CIs)is of utmost importance,but is *** intended to quantitatively characterize the posttranslational modification status of CIs of antibody drugs and explore the impact of posttranslational modifications on charge *** CIs of antibodies were fractionated by strong cation exchange chromatography and verified by capillary isoelectric focusing-whole column imaging detection,followed by stepwise structural characterization at three ***,the differences between CIs were explored at the intact protein level using a top-down mass spectrometry approach;this showed differences in glycoforms and deamidation ***,at the peptide level,common modifications of oxidation,deamidation,and glycosylation were *** mapping showed nonuniform deamidation and glycoform distribution among *** total,10 N-glycoforms were detected by peptide ***,an in-depth analysis of glycan variants of CIs was performed through the detection of enriched *** and quantitative analyses demonstrated the dynamics of 24 *** results revealed that sialic acid modification is a critical factor accounting for charge heterogeneity,which is otherwise missed in peptide mapping and intact molecular weight *** study demonstrated the importance of the comprehensive analyses of antibody CIs and provides a reference method for the quality control of biopharmaceutical analysis.

关键词： Antibody Charge isomers Mass spectrometry posttranslational modification Glycopeptide

Targeting the PD-L1 cytoplasmic domain and its regulatory pathways to enhance cancer immunotherapy

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Journal of Molecular Cell Biology 2023年第11期15卷 12-20页

作者： Fangni Chai Pan Li Xin Liu Zhihui Zhou Haiyan Ren Division of Respiratory and Critical Care Medicine West China Hospital of Sichuan UniversityChengdu 610041China Collaborative Innovation Center of Biotherapy Chengdu 610041China

As a significant member of the immune checkpoint,programmed cell death 1 ligand 1(PD-L1)plays a critical role in cancer immune escape and has become an important target for cancer *** approved drugs mainly target the extracellular domain of ***,the small cytoplasmic domain of PD-L1 has been reported to regulate PD-L1 stability and function through multiple ***,the intracellular domain of PD-L1 and its regulatory pathways could be promising targets for cancer therapy,expanding available strategies for combined ***,we summarize the emerging roles of the PD-L1 cytoplasmic domain and its regulatory *** conserved motifs,homodimerization,and posttranslational modifications ofthe PD-L1 cytoplasmic domain have been reported to regulate the membrane anchoring,degradation,nucleartranslocation,and glycosylation of *** summary provides a comprehensive understanding of the functions of the PD-L1 cytoplasmic domain and evaluates the broad prospects for targeted therapy.

关键词： PD-L1 cytoplasmic domain immunotherapy posttranslational modification

posttranslational regulation of androgen dependent and independent androgen receptor activities in prostate cancer

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Asian Journal of Urology 2020年第3期7卷 203-218页

作者： Simeng Wen Yuanjie Niu Haojie Huang Department of Urology The Second Hospital of Tianjin Medical UniversityTianjin Institute of UrologyTianjin Medical UniversityTianjinChina Department of Biochemistry and Molecular Biology Mayo Clinic College of Medicine and ScienceRochesterUSA Department of Urology Mayo Clinic College of Medicine and ScienceRochesterUSA Mayo Clinic Cancer Center Mayo Clinic College of Medicine and ScienceRochesterUSA

Prostate cancer(PCa)is the most commonly diagnosed cancer among men in western *** receptor(AR)signaling plays key roles in the development of *** deprivation therapy(ADT)remains the standard therapy for advanced *** addition to its ligand androgen,accumulating evidence indicates that posttranscriptional modification is another important mechanism to regulate AR activities during the progression of PCa,especially in castration resistant prostate cancer(CRPC).To date,a number of posttranscriptional modifications of AR have been identified,including phosphorylation(*** CDK1),acetylation(*** p300 and recognized by BRD4),methylation(*** EZH2),ubiquitination(*** SPOP),and SUMOylation(*** PIAS1).These modifications are essential for the maintenance of protein stability,nuclear localization and transcriptional activity of *** review summarizes posttranslational modifications that influence androgen-dependent and-independent activities of AR,PCa progression and therapy *** further emphasize that in addition to androgen,posttranslational modification is another important way to regulate AR activity,suggesting that targeting AR posttranslational modifications,such as proteolysis targeting chimeras(PROTACs)of AR,represents a potential and promising alternate for effective treatment of *** areas to be investigated in the future in the field of AR posttranslational modifications are also discussed.

关键词： Androgen receptor posttranslational modification Phosphorylation Acetylation Methylation Ubiquitination SUMOylation PROTAC SPOP Prostate cancer

Th17 Cells in autoimmune diseases

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Frontiers of Medicine 2015年第1期9卷 10-19页

作者： Lei Han Jing Yang Xiuwen Wang Dan Li Ling Lv Bin Li Division of Rheumatology Huashan Hospital Fudan University Shanghai 200040 China Key Laboratory of Molecular Virology and Immunology Unit of Molecular Immunology Institut Pasteur of Shanghai Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200032 China

Th17 cells are a new subset of CD4^＋ T cells fungi. Accumulating evidence suggests that Tb17 cells involved in the clearance of extracellular pathogens and and their signature cytokines have a pivotal role in the pathogenesis of multiple autoimmune-mediated inflammatory diseases. Here, we summarize recent research progress on Th17 function in the development and pathogenesis of autoimmune diseases. We also propose to identify new small molecule compounds to manipulate Th17 function for potential therapeutic application to treat human autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, Sjogren＇s syndrome, inflammatory bowel disease, and multiple sclerosis.

关键词： IL-17 Thl 7 cells RORγt autoimmune diseases posttranslational modification inhibitors

Cell biology and immunology lessons taught by Legionella pneumophila

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Science China(Life Sciences) 2016年第1期59卷 3-10页

作者： Wenhan Zhu Zhao-Qing Luo Department of Biological Sciences Purdue University Department of Microbiology UT Southwestern Medical Center

Legionella pneumophila is a facultative intracellular pathogen capable of replicating within a broad range of hosts. One unique feature of this pathogen is the cohort of ca. 300 virulence factors(effectors) delivered into host cells via its Dot/Icm type IV secretion system. Study of these proteins has produced novel insights into the mechanisms of host function modulation by pathogens, the regulation of essential processes of eukaryotic cells and of immunosurveillance. In this review, we will briefly discuss the roles of some of these effectors in the creation of a niche permissive for bacterial replication in phagocytes and recent advancements in the dissection of the innate immune detection mechanisms by challenging immune cells with L. pneumophila.

关键词： Type IV secretion inflammasome effectors posttranslational modification vesicle transport

O-linked β-N-acetylglucosamine modification and its biological functions

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Science Bulletin 2015年第12期60卷 1055-1061,I0002页

作者： Yan Liu Shaojun Dai Lijing Xing Yunyuan Xu Kang Chong Alkali Soil Natural Environmental Science Center NortheastForestry University Key Laboratory of Saline-Alkali VegetationEcology Restoration in Oil Field Ministry of Education Harbin150040 China Key Laboratory of Plant Molecular Physiology Institute ofBotany Chinese Academy of Sciences Beijing 100093 China

The covalent attachment of O-linked β-N- acetylglucosamine （O-GIcNAc） to Ser/Thr residues of proteins acts as not only a posttranslational modification but also a nutritional sensor in nucleus and cytoplasm, which directly regulates the expression of genes and multiple crucial signal transduction pathways. Dynamic O- GlcNAcylation at Ser/Thr residues is catalyzed by two key enzymes, O-GIcNAc transferase （OGT） and O-GlcNAcase, which are responsible for addition and removal of the O- GlcNAc modification, respectively. O-GlcNAc modifica- tion plays important roles in cellular signaling in animals, especially in human diseases. Two orthologs of OGT in plants, SECRET AGENT and SPINDLY, have been reported to be involved in diverse plant processes. However, compared with the functional mechanisms revealed in animals, the consequences of protein O-GlcNAc modifi- cation in plants is largely unknown, and the relationship between O-GlcNAcylation and cellular processes needs to be explored. In this review, we summarized the recent advances on O-GlcNAc modification and its biological functions in animals and plants, and prospect of more special functions of O-GlcNAc will be revealed in plants.

关键词： O-GlcNAc posttranslational modification Epigenetic regulation Plants

Deciphering the PTM codes of the tumor suppressor p53

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Journal of Molecular Cell Biology 2021年第11期13卷 774-785页

作者： Jia Wen Donglai Wang State Key Laboratory of Medical Molecular Biology&Department of Medical Genetics Institute of Basic Medical Sciences&School of Basic MedicineChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100005China

The genome guardian p53 functions as a transcription factor that senses numerous cellular stresses and orchestrates the corresponding transcriptional events involved in determining various cellular outcomes,including cell cycle arrest,apoptosis,senescence,DNA repair,and metabolic *** response to diverse stresses,p53 undergoes multiple posttranslational modifications(PTMs)that coordinate with intimate interdependencies to precisely modulate its diverse properties in given biological ***,PTMs can recruit‘reader’proteins that exclusively recognize specific modifications and facilitate the functional readout of *** PTM–reader interplay has been developing into a promising cancer therapeutic *** this review,we summarize the advances in deciphering the‘PTM codes’of p53,focusing particularly on the mechanisms by which the specific reader proteins functionally decipher the information harbored within these PTMs of *** also highlight the potential applications of intervention with p53 PTM–reader interactions in cancer therapy and discuss perspectives on the‘PTMomic’study of p53 and other proteins.

关键词： p53 posttranslational modification reader PTM code tumor therapy