Coronavirus disease 2019(COVID-19),a highly infectious disease caused by severe acute respiratory syndrome coronavirus 2(SARSCoV-2),has infected more than 235 million individuals and led to more than 4.8 million death...Coronavirus disease 2019(COVID-19),a highly infectious disease caused by severe acute respiratory syndrome coronavirus 2(SARSCoV-2),has infected more than 235 million individuals and led to more than 4.8 million deaths worldwide as of October 52021.Cryo-electron microscopy and topology show that the SARS-CoV-2 genome encodes lots of highly glycosylated proteins,such as spike(S),envelope(E),membrane(M),and ORF3a proteins,which are responsible for host recognition,penetration,binding,recycling and pathogenesis.Here we reviewed the detections,substrates,biological functions of the glycosylation in SARS-CoV-2 proteins as well as the human receptor ACE2,and also summarized the approved and undergoing SARS-CoV-2 therapeutics associated with glycosylation.This review may not only broad the understanding of viral glycobiology,but also provide key clues for the development of new preventive and therapeutic methodologies against SARS-CoV-2 and its variants.展开更多
Currently,drug resistance of anti-cancer therapy has become the main cause of low survival rate and poor prognosis.Full understanding of drug resistance mechanisms is an urgent request for further development of anti-...Currently,drug resistance of anti-cancer therapy has become the main cause of low survival rate and poor prognosis.Full understanding of drug resistance mechanisms is an urgent request for further development of anti-cancer therapy and improve-ment of prognosis.Here we present our N-glycoproteomics study of putative N-glycoprotein biomarkers of drug resistance in doxorubicin resistance breast cancer cell line michigan cancer foundation-7(MCF-7/ADR)relative to parental michigan cancer foundation-7(MCF-7)cells.Intact N-glycopeptides(IDs)from MCF-7/ADR and MCF-7 cells were enriched with zwitterionic hydrophilic interaction liquid chromatography(ZIC-HILIC),labeled with stable isotopic diethylation(SIDE),and analyzed with C18-RPLC-MS/MS(HCD with stepped normalized collision energies);these IDs were identified with database search engine GPSeeker,and the differentially expressed intact N-glycopeptides(DEGPs)were quantified with GPSeekerQuan.With target-decoy searches and control of spectrum-level FDR≤1%,322 intact N-glycopeptides were identified;these intact N-glycopeptides come from the combination of 249 unique peptide backbones(corresponding to 234 intact N-glycoproteins)and 90 monosaccharide compositions(corresponding to 248 putative N-glycosites).The sequence structures of 165 IDs were confirmed with structure-diagnostic fragment ions.With the criteria of observation at least twice among the three technical replicates,≥1.5-fold change and p value<0.05,20 DEGPs were quantified,where five of them were up-regulated and 15 of them were down-regulated;the corresponding intact N-glycoproteins as putative markers of drug resistance were discussed.展开更多
O-linkedβ-N-acetylglucosaminylation(O-GlcNAcylation)is a highly dynamic and widespread post-translational modification(PTM)that regulates the activity,subcellular localization,and stability of target proteins.O-GlcNA...O-linkedβ-N-acetylglucosaminylation(O-GlcNAcylation)is a highly dynamic and widespread post-translational modification(PTM)that regulates the activity,subcellular localization,and stability of target proteins.O-GlcNAcylation is a reversible PTM controlled by two cycling enzymes:O-linked N-acetylglucosamine transferase and O-GlcNAcase.Emerging evidence indicates that O-GlcNAcylation plays critical roles in innate immunity,inflammatory signaling,and cancer development.O-GlcNAcylation usually occurs on serine/threonine residues,where it interacts with other PTMs,such as phosphorylation.Thus,it likely has a broad regulatory scope.This review discusses the recent research advances regarding the regulatory roles of O-GlcNAcylation in innate immunity and inflammation.A more comprehensive understanding ofO-GlcNAcylation could help to optimize therapeutic strategies regarding inflammatory diseases and cancer.展开更多
基金This work was supported by the National Key R&D Program of China(No.2018YFC2000305 and 2018YFC1312301)National Natural Science Foundation of China(No.81570060,31870826,82073221,21775110,and 22074105)+2 种基金the program of National Clinical Research Center for Geriatrics of West China Hospital(No.Z20191001)West China Hospital 1.3.5 project for disciplines of excellence(No.ZYYC20007)Shanghai Science and Technology Commission(14DZ2261100).
文摘Coronavirus disease 2019(COVID-19),a highly infectious disease caused by severe acute respiratory syndrome coronavirus 2(SARSCoV-2),has infected more than 235 million individuals and led to more than 4.8 million deaths worldwide as of October 52021.Cryo-electron microscopy and topology show that the SARS-CoV-2 genome encodes lots of highly glycosylated proteins,such as spike(S),envelope(E),membrane(M),and ORF3a proteins,which are responsible for host recognition,penetration,binding,recycling and pathogenesis.Here we reviewed the detections,substrates,biological functions of the glycosylation in SARS-CoV-2 proteins as well as the human receptor ACE2,and also summarized the approved and undergoing SARS-CoV-2 therapeutics associated with glycosylation.This review may not only broad the understanding of viral glycobiology,but also provide key clues for the development of new preventive and therapeutic methodologies against SARS-CoV-2 and its variants.
基金supported by National Natural Science Foundation of China(21775110,22074105)Shanghai Science and Technology Commission(14DZ2261100).
文摘Currently,drug resistance of anti-cancer therapy has become the main cause of low survival rate and poor prognosis.Full understanding of drug resistance mechanisms is an urgent request for further development of anti-cancer therapy and improve-ment of prognosis.Here we present our N-glycoproteomics study of putative N-glycoprotein biomarkers of drug resistance in doxorubicin resistance breast cancer cell line michigan cancer foundation-7(MCF-7/ADR)relative to parental michigan cancer foundation-7(MCF-7)cells.Intact N-glycopeptides(IDs)from MCF-7/ADR and MCF-7 cells were enriched with zwitterionic hydrophilic interaction liquid chromatography(ZIC-HILIC),labeled with stable isotopic diethylation(SIDE),and analyzed with C18-RPLC-MS/MS(HCD with stepped normalized collision energies);these IDs were identified with database search engine GPSeeker,and the differentially expressed intact N-glycopeptides(DEGPs)were quantified with GPSeekerQuan.With target-decoy searches and control of spectrum-level FDR≤1%,322 intact N-glycopeptides were identified;these intact N-glycopeptides come from the combination of 249 unique peptide backbones(corresponding to 234 intact N-glycoproteins)and 90 monosaccharide compositions(corresponding to 248 putative N-glycosites).The sequence structures of 165 IDs were confirmed with structure-diagnostic fragment ions.With the criteria of observation at least twice among the three technical replicates,≥1.5-fold change and p value<0.05,20 DEGPs were quantified,where five of them were up-regulated and 15 of them were down-regulated;the corresponding intact N-glycoproteins as putative markers of drug resistance were discussed.
基金The current work was supported by a special program from the Ministry of Science and Technology of China(2021YFA1101000)the National Natural Science Foundation of China(U20A20393,32125016,31871405,31925013,31870902,and 32070907)+1 种基金Jiangsu National Science Foundation(19KJA550003)a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘O-linkedβ-N-acetylglucosaminylation(O-GlcNAcylation)is a highly dynamic and widespread post-translational modification(PTM)that regulates the activity,subcellular localization,and stability of target proteins.O-GlcNAcylation is a reversible PTM controlled by two cycling enzymes:O-linked N-acetylglucosamine transferase and O-GlcNAcase.Emerging evidence indicates that O-GlcNAcylation plays critical roles in innate immunity,inflammatory signaling,and cancer development.O-GlcNAcylation usually occurs on serine/threonine residues,where it interacts with other PTMs,such as phosphorylation.Thus,it likely has a broad regulatory scope.This review discusses the recent research advances regarding the regulatory roles of O-GlcNAcylation in innate immunity and inflammation.A more comprehensive understanding ofO-GlcNAcylation could help to optimize therapeutic strategies regarding inflammatory diseases and cancer.