Core 1 synthase glycoprotein-N-acetylgalactosamine 3-β-galactosyltransferase 1(C1GALT1)is known to play a critical role in the development of gastric cancer,but few studies have elucidated associations between geneti...Core 1 synthase glycoprotein-N-acetylgalactosamine 3-β-galactosyltransferase 1(C1GALT1)is known to play a critical role in the development of gastric cancer,but few studies have elucidated associations between genetic variants in C1GALT1 and gastric cancer risk.By using the genome-wide association study data from the database of Genotype and Phenotype(dbGAP),we evaluated such associations with a multivariable logistic regression model and identified that the rs35999583 G>C in C1GALT1 was associated with gastric cancer risk(odds ratio,0.83;95% confidence interval[CI],0.75-0.92;P=3.95×10^(-4)).C1GALT1 mRNA expression levels were significantly higher in gastric tumor tissues than in normal tissues,and gastric cancer patients with higher C1GALT1 mRNA levels had worse overall survival rates(hazards ratio,1.33;95%CI,1.05-1.68;P_(log-rank)=1.90×10^(-2)).Furthermore,we found that C1GALT1 copy number differed in various immune cells and that C1GALT1 mRNA expression levels were positively correlated with the infiltrating levels of CD4^(+)T cells and macrophages.These results suggest that genetic variants of C1GALT1 may play an important role in gastric cancer risk and provide a new insight for C1GALT1 into a promising predictor of gastric cancer susceptibility and immune status.展开更多
O-glycosylation is an ancient yet underappreciated protein posttranslational modification,on which many bacteria and viruses heavily rely to perform critical biological functions involved in numerous infectious diseas...O-glycosylation is an ancient yet underappreciated protein posttranslational modification,on which many bacteria and viruses heavily rely to perform critical biological functions involved in numerous infectious diseases or even cancer.But due to the innate complexity of O-glycosylation,research techniques have been limited to study its exact role in viral attachment and entry,assembly and exit,spreading in the host cells,and the innate and adaptive immunity of the host.Recently,the advent of many newly developed methodologies(e.g.,mass spectrometry,chemical biology tools,and molecular dynamics simulations)has renewed and rekindled the interest in viral-related O-glycosylation in both viral proteins and host cells,which is further fueled by the COVID-19 pandemic.In this review,we summarize recent advances in viral-related O-glycosylation,with a particular emphasis on the mucin-type O-linkedα-N-acetylgalactosamine(O-GalNAc)on viral proteins and the intracellular O-linkedβ-N-acetylglucosamine(O-GlcNAc)modifications on host proteins.We hope to provide valuable insights into the development of antiviral reagents or vaccines for better prevention or treatment of infectious diseases.展开更多
A hydrogen bond-assisted α-selective glycosylation reaction by using 4,6-dibenzyloxy-1,3,5-triazin-2-yl(DBT) β-glycosyl donors was developed for the efficient construction of 1,2-cis-α-glycosidic bond in natural pr...A hydrogen bond-assisted α-selective glycosylation reaction by using 4,6-dibenzyloxy-1,3,5-triazin-2-yl(DBT) β-glycosyl donors was developed for the efficient construction of 1,2-cis-α-glycosidic bond in natural products. This method was applied successfully to the direct synthesis of complex oligosaccharidederived glycolipids with simple protecting chemistry. Mechanistic studies using the NMR spectroscopy and DFT calculation provide a proof of concept for hydrogen bond-assisted glycosylation reaction towardsα-specific construction of O-glycosidic linkage.展开更多
Post-translational protein modification, including phosphorylation, is generally quick and reversible, facilitating rapid biologic adjustments to altered cellular physiologic demands. In addition to protein phosphoryl...Post-translational protein modification, including phosphorylation, is generally quick and reversible, facilitating rapid biologic adjustments to altered cellular physiologic demands. In addition to protein phosphorylation, other post-translational modifications have been identified. Intracellular protein O-glycosylation, the addition of the simple sugar O-linked N-acetylglucosamine （O-G1cNAc） to serine/threonine residues, is a relatively recently identified post-translational modification that has added to the complexity by which protein function is regulated. Two intracellular enzymes, O-GlcNAc transferase and O-GlcNAcase, catalyze the addition and removal, respectively, of O-GlcNAc to serine and threonine side-chain hydroxyl groups. Numerous proteins, including enzymes, transcription factors, receptors and structural proteins have been shown to be modified by intracellular O-glycosylation. In this review, the mechanism and relevance of O-GlcNAc protein modification are discussed in the context of cell adhesion and several representative diseases.展开更多
法尼酯X受体(farnesoid X receptor,FXR)是一种由胆汁酸激活的核受体,参与调控胆汁酸、脂肪、葡萄糖和氨基酸代谢相关的基因表达,FXR活性受到多种翻译后修饰方式的调控。常见FXR翻译后修饰方式包括O-糖基化、磷酸化、乙酰化、SUMO化和...法尼酯X受体(farnesoid X receptor,FXR)是一种由胆汁酸激活的核受体,参与调控胆汁酸、脂肪、葡萄糖和氨基酸代谢相关的基因表达,FXR活性受到多种翻译后修饰方式的调控。常见FXR翻译后修饰方式包括O-糖基化、磷酸化、乙酰化、SUMO化和甲基化等,这些翻译后修饰方式可能影响FXR结合DNA和配体、异源二聚化和亚细胞定位等功能,可能特异性调控下游基因转录表达。不同翻译后修饰可导致FXR稳定性及生物学功能改变,与疾病的发生密切相关。本文拟对近5年FXR的翻译后修饰方式及参与疾病调控的机制作一综述,探讨翻译后修饰方式对FXR生理学功能的影响,为以FXR为靶点的机制研究提供理论依据。展开更多
基金funded by the National Key R&D Program of China(Grant Nos.2018YFC1313100 and 2018YFC1313102)the National Natural Science Foundation of China(Grant No.81773539)+1 种基金Collaborative Innovation Center for Cancer Personalized Medicinethe Priority Academic Program Development of Jiangsu Higher Education Institutions(Public Health and Preventive Medicine).
文摘Core 1 synthase glycoprotein-N-acetylgalactosamine 3-β-galactosyltransferase 1(C1GALT1)is known to play a critical role in the development of gastric cancer,but few studies have elucidated associations between genetic variants in C1GALT1 and gastric cancer risk.By using the genome-wide association study data from the database of Genotype and Phenotype(dbGAP),we evaluated such associations with a multivariable logistic regression model and identified that the rs35999583 G>C in C1GALT1 was associated with gastric cancer risk(odds ratio,0.83;95% confidence interval[CI],0.75-0.92;P=3.95×10^(-4)).C1GALT1 mRNA expression levels were significantly higher in gastric tumor tissues than in normal tissues,and gastric cancer patients with higher C1GALT1 mRNA levels had worse overall survival rates(hazards ratio,1.33;95%CI,1.05-1.68;P_(log-rank)=1.90×10^(-2)).Furthermore,we found that C1GALT1 copy number differed in various immune cells and that C1GALT1 mRNA expression levels were positively correlated with the infiltrating levels of CD4^(+)T cells and macrophages.These results suggest that genetic variants of C1GALT1 may play an important role in gastric cancer risk and provide a new insight for C1GALT1 into a promising predictor of gastric cancer susceptibility and immune status.
基金supported by the grants from the National Natural Science Foundation of China(32271285,31872720,82272306,and 82072270)the R&D Program of Beijing Municipal Education Commission(KZ202210028043)+3 种基金the Taishan Scholars Program(tstp20221142)the Academic Promotion Program of Shandong First Medical University(2019LJ001)the Beijing National LaboratorfyorMolecular Sciences(BNLMS202108)the Chinese Academy of Sciences Pioneer Hundred Talents Program.
文摘O-glycosylation is an ancient yet underappreciated protein posttranslational modification,on which many bacteria and viruses heavily rely to perform critical biological functions involved in numerous infectious diseases or even cancer.But due to the innate complexity of O-glycosylation,research techniques have been limited to study its exact role in viral attachment and entry,assembly and exit,spreading in the host cells,and the innate and adaptive immunity of the host.Recently,the advent of many newly developed methodologies(e.g.,mass spectrometry,chemical biology tools,and molecular dynamics simulations)has renewed and rekindled the interest in viral-related O-glycosylation in both viral proteins and host cells,which is further fueled by the COVID-19 pandemic.In this review,we summarize recent advances in viral-related O-glycosylation,with a particular emphasis on the mucin-type O-linkedα-N-acetylgalactosamine(O-GalNAc)on viral proteins and the intracellular O-linkedβ-N-acetylglucosamine(O-GlcNAc)modifications on host proteins.We hope to provide valuable insights into the development of antiviral reagents or vaccines for better prevention or treatment of infectious diseases.
基金financially supported by the State Key Laboratory of Natural and Biomimetic Drugs (No. K202216)the National Natural Science Foundation of China (Nos. 21907004 and 81821004)+2 种基金the National Key R&D Program of China (No.2018YFA0507602)the Beijing Outstanding Young Scientist Program(No. BJJWZYJH01201910001001)a Grant-in-Aid for Scientific Research from the Ministry of Education,Culture,Sports,Science and Technology,Japan。
文摘A hydrogen bond-assisted α-selective glycosylation reaction by using 4,6-dibenzyloxy-1,3,5-triazin-2-yl(DBT) β-glycosyl donors was developed for the efficient construction of 1,2-cis-α-glycosidic bond in natural products. This method was applied successfully to the direct synthesis of complex oligosaccharidederived glycolipids with simple protecting chemistry. Mechanistic studies using the NMR spectroscopy and DFT calculation provide a proof of concept for hydrogen bond-assisted glycosylation reaction towardsα-specific construction of O-glycosidic linkage.
基金supported by NIH RO1 (No. AI49427) to Dr David S.Rubenstein
文摘Post-translational protein modification, including phosphorylation, is generally quick and reversible, facilitating rapid biologic adjustments to altered cellular physiologic demands. In addition to protein phosphorylation, other post-translational modifications have been identified. Intracellular protein O-glycosylation, the addition of the simple sugar O-linked N-acetylglucosamine （O-G1cNAc） to serine/threonine residues, is a relatively recently identified post-translational modification that has added to the complexity by which protein function is regulated. Two intracellular enzymes, O-GlcNAc transferase and O-GlcNAcase, catalyze the addition and removal, respectively, of O-GlcNAc to serine and threonine side-chain hydroxyl groups. Numerous proteins, including enzymes, transcription factors, receptors and structural proteins have been shown to be modified by intracellular O-glycosylation. In this review, the mechanism and relevance of O-GlcNAc protein modification are discussed in the context of cell adhesion and several representative diseases.
文摘法尼酯X受体(farnesoid X receptor,FXR)是一种由胆汁酸激活的核受体,参与调控胆汁酸、脂肪、葡萄糖和氨基酸代谢相关的基因表达,FXR活性受到多种翻译后修饰方式的调控。常见FXR翻译后修饰方式包括O-糖基化、磷酸化、乙酰化、SUMO化和甲基化等,这些翻译后修饰方式可能影响FXR结合DNA和配体、异源二聚化和亚细胞定位等功能,可能特异性调控下游基因转录表达。不同翻译后修饰可导致FXR稳定性及生物学功能改变,与疾病的发生密切相关。本文拟对近5年FXR的翻译后修饰方式及参与疾病调控的机制作一综述,探讨翻译后修饰方式对FXR生理学功能的影响,为以FXR为靶点的机制研究提供理论依据。
