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sialylation is involved in cell fate decision during development, reprogramming and cancer progression

Protein & Cell 2019年第8期10卷 550-565页

作者： Fenjie Li Junjun Ding Program in Stem Cell and Regenerative Medicine The Third Affiliated Hospital of Sun Yat-Sen University Zhongshan School of Medicine Sun Yat-Sen University Guangzhou China Key Laboratory for Stem Cells and Tissue Engineering Ministry of Education Department of Cell Biology Zhongshan School of Medicine Sun Yat-Sen University Guangzhou China

sialylation, or the covalent addition of sialic acid to the terminal end of glycoproteins, is a biologically important modification that is involved in embryonic development, neurodevelopment, reprogramming, oncogenesis and immune responses. In this review, we have given a comprehensive overview of the current literature on the involvement of sialylation in cell fate decision during development, reprogramming and cancer progressionsialylation is essential for early embryonic development and the deletion of UDP-GIcNAc 2-epimerase, a rate-limiting enzyme in sialic acid biosynthesis, is embryonically lethal. Furthermore, the sialyltransferase ST6GAL1 is required for somatic cell reprogramming, and its downregulation is associated with decreased reprogramming efficiency. In addition, sialylation levels and patterns are altered during cancer progression, indicating the potential of sialylated molecules as cancer biomarkers. Taken together, the current evidences demonstrate that sialylation is involved in crucial cell fate decision.

关键词： sialylation cell fate development reprogramming cancer

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Fragmentation stability and retention time-shift obtained by LC-MS/MS to distinguish sialylated N-glycan linkage isomers in therapeutic glycoproteins

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Journal of Pharmaceutical Analysis 2023年第3期13卷 305-314页

作者： Chi Soo Park Minju Kang Ahyeon Kim Chulmin Moon Mirae Kim Jieun Kim Subin Yang Leeseul Jang Ji Yeon Jang Ha Hyung Kim Department of Global Innovative Drugs Graduate School of Chung-Ang UniversitySeoul06974Republic of Korea

Sialylated N-glycan isomers withα2-3 orα2-6 linkage(s)have distinctive roles in glycoproteins,but are difficult to ***-type(WT)and glycoengineered(mutant)therapeutic glycoproteins,cytotoxic T lymphocyte-associated antigen-4-immunoglobulin(CTLA4-Ig),were produced in Chinese hamster ovary cell lines;however,their linkage isomers have not been *** this study,N-glycans of CTLA4-Igs were released,labeled with procainamide,and analyzed by liquid chromatography-tandem mass spectrometry(MS/MS)to identify and quantify sialylated N-glycan linkage *** linkage isomers were distinguished by comparison of 1)intensity of the N-acetylglucosamine ion to the sialic acid ion(Ln/Nn)using different fragmentation stability in MS/MS spectra and 2)retention time-shift for a selective m/z value in the extracted ion *** isomer was distinctively identified,and each quantity(>0.1%)was obtained relative to the total N-glycans(100%)for all observed ionization *** sialylated N-glycan isomers with onlyα2-3 linkage(s)in WT were identified,and each isomer's sum of quantities was 50.4%.Furthermore,39 sialylated N-glycan isomers(58.8%)in mono-(3 N-glycans;0.9%),bi-(18;48.3%),tri-(14;8.9%),and tetra-(4;0.7%)antennary structures of mutant were obtained,which comprised mono-(15 N-glycans;25.4%),di-(15;28.4%),tri-(8;4.8%),and tetra-(1;0.2%)sialylation,respectively,with onlyα2-3(10 N-glycans;4.8%),bothα2-3 andα2-6(14;18.4%),and onlyα2-6(15;35.6%)linkage(s).These results are consistent with those forα2-3 neuraminidase-treated *** study generated a novel plot of Ln/Nn versus retention time to distinguish sialylated N-glycan linkage isomers in glycoprotein.

关键词： Therapeutic glycoprotein sialylation Linkage isomer LC-MS/MS

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Chemoenzymatic synthesis of α2–3-sialylated carbohydrate epitopes

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Science China Chemistry 2011年第1期54卷 117-128页

作者： HUANG ShengShu YU Hai CHEN Xi Department of Chemistry University of California One Shields Avenue Davis California 95616 USA

Sialic acids are common terminal carbohydrates on cell *** with internal carbohydrate structures,they play important roles in many physiological and pathological *** order to obtain α2–3-sialylated oligosaccharides,a highly efficient one-pot three-enzyme synthetic approach was *** *** α2–3-sialyltransferase (PmST1) involved in the synthesis was a multifunctional enzyme with extremely flexible donor and acceptor substrate *** acceptors,including type 1 structure (Galβ1–3GlcNAcβProN3),type 2 structures (Galβ1–4GlcNAcβProN3 and 6-sulfo-Galβ1– 4GlcNAcβProN3),type 4 structure (Galβ1–3GalNAcβProN3),type 3 or core 1 structure (Galβ1–3GalNAcβProN3) and human milk oligoscaccharide or lipooligosaccharide lacto-N-tetraose (LNT) (Galβ1–3GlcNAcβ1–3Galβ1–4GlcβProN3),were chemically *** were then used in one-pot three-enzyme reactions with sialic acid precursor ManNAc or ManNGc,to synthesize a library of naturally occurring β2–3-linked sialosides with different internal sugar *** sialylated oligosaccharides obtained are valuable probes for their biological studies.

关键词： carbohydrate chemoenzymatic synthesis sialic acid sialylation sialyltransferase

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ST6GAL1 inhibits the hepatocellular carcinoma intrahepatic metastasis

ST6GAL1 inhibits the hepatocellular carcinoma intrahepatic m...

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2020年糖科学青年科技论坛

作者：邹霞陆吉顺张延上海交通大学系统生物医学研究院教育部重点实验室

The poor prognosis of hepatocellular carcinoma(HCC) is mainly due to its high rate of ***,elucidation of the molecular mechanisms underlying HCC metastasis is of great significance to improve the survival rate of HCC *** is an important post-translational modification,which is closely associated with the tumor *** glycosylation including the altered sialylation resulting from the aberrant expression of sialyltransferase like β-Galactoside α2,6 sialyltranferase 1(ST6 GAL1) have long been considered as an important feature of cancer ***,there is limited information on the molecular details of how ST6 GAL1 catalyzed glycan structures affect their carrier proteins during tumor *** this study,we systematically investigated the role of ST6 GAL1 in HCC metastasis and found that ST6 GAL1 can inhibit the metastasis of HCC in vitro and in vivo using lectin microarray,glycogene microarray and mouse ***,about 300 potential substrate membrane proteins of ST6 GAL1 were identified by metabolic labeling and MS analysis,and some of them were verified in cell models and clinical *** together,this study provides novel insight into the mechanistic roles of ST6 GAL1 in HCC progression.

关键词： ST6GAL1 sialylation Metastasis HCC

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