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Cells May 2021Evading host immune surveillance is one of the hallmarks of cancer. Immune checkpoint therapy, which aims to eliminate cancer progression by reprogramming the antitumor... (Review)
Review
Evading host immune surveillance is one of the hallmarks of cancer. Immune checkpoint therapy, which aims to eliminate cancer progression by reprogramming the antitumor immune response, currently occupies a solid position in the rapidly expanding arsenal of cancer therapy. As most immune checkpoints are membrane glycoproteins, mounting attention is drawn to asking how protein glycosylation affects immune function. The answers to this fundamental question will stimulate the rational development of future cancer diagnostics and therapeutic strategies.
Topics: Animals; Glycosylation; Humans; Immune Checkpoint Inhibitors; Neoplasms; Protein Processing, Post-Translational; Receptors, Immunologic
PubMed: 34064396
DOI: 10.3390/cells10051100 -
Current Opinion in Structural Biology Apr 2023Glycosyltransferases of the C superfamily (GT-Cs) are enzymes found in all domains of life. They catalyse the stepwise synthesis of oligosaccharides or the transfer of... (Review)
Review
Glycosyltransferases of the C superfamily (GT-Cs) are enzymes found in all domains of life. They catalyse the stepwise synthesis of oligosaccharides or the transfer of assembled glycans from lipid-linked donor substrates to acceptor proteins. The processes mediated by GT-Cs are required for C-, N- and O-linked glycosylation, all of which are essential post-translational modifications in higher-order eukaryotes. Until recently, GT-Cs were thought to share a conserved structural module of 7 transmembrane helices; however, recently determined GT-C structures revealed novel folds. Here we analyse the growing diversity of GT-C folds and discuss the emergence of two subclasses, termed GT-C and GT-C. Further substrate-bound structures are needed to facilitate a molecular understanding of glycan recognition and catalysis in these two subclasses.
Topics: Glycosyltransferases; Glycosylation; Polysaccharides; Oligosaccharides; Protein Structure, Secondary
PubMed: 36827761
DOI: 10.1016/j.sbi.2023.102547 -
Cardiovascular Research Mar 2021Protein glycosylation is a post-translational modification consisting in the enzymatic attachment of carbohydrate chains to specific residues of the protein sequence.... (Review)
Review
Protein glycosylation is a post-translational modification consisting in the enzymatic attachment of carbohydrate chains to specific residues of the protein sequence. Several types of glycosylation have been described, with N-glycosylation and O-glycosylation being the most common types impacting on crucial biological processes, such as protein synthesis, trafficking, localization, and function. Genetic defects in genes involved in protein glycosylation may result in altered production and activity of several proteins, with a broad range of clinical manifestations, including dyslipidaemia and atherosclerosis. A large number of apolipoproteins, lipoprotein receptors, and other proteins involved in lipoprotein metabolism are glycosylated, and alterations in their glycosylation profile are associated with changes in their expression and/or function. Rare genetic diseases and population genetics have provided additional information linking protein glycosylation to the regulation of lipoprotein metabolism.
Topics: Animals; Apolipoproteins; Atherosclerosis; Dyslipidemias; Genetic Predisposition to Disease; Glycosylation; Humans; Lipid Metabolism; Lipoproteins; Phenotype; Plaque, Atherosclerotic; Protein Processing, Post-Translational; Receptors, Lipoprotein
PubMed: 32886765
DOI: 10.1093/cvr/cvaa252 -
Biomolecules Sep 2022This article is part of the Special Issue Glycosylation-The Most Diverse Post-Translational Modification [...].
This article is part of the Special Issue Glycosylation-The Most Diverse Post-Translational Modification [...].
Topics: Glycosylation; Protein Processing, Post-Translational
PubMed: 36139152
DOI: 10.3390/biom12091313 -
BMB Reports Nov 2021Protein glycosylation is a common post-translational modification found in all living organisms. This modification in bacterial pathogens plays a pivotal role in their... (Review)
Review
Protein glycosylation is a common post-translational modification found in all living organisms. This modification in bacterial pathogens plays a pivotal role in their infectious processes including pathogenicity, immune evasion, and host-pathogen interactions. Importantly, many key proteins of host immune systems are also glycosylated and bacterial pathogens can notably modulate glycosylation of these host proteins to facilitate pathogenesis through the induction of abnormal host protein activity and abundance. In recent years, interest in studying the regulation of host protein glycosylation caused by bacterial pathogens is increasing to fully understand bacterial pathogenesis. In this review, we focus on how bacterial pathogens regulate remodeling of host glycoproteins during infections to promote the pathogenesis. [BMB Reports 2021; 54(11): 541-544].
Topics: Animals; Bacteria; Bacterial Infections; Glycoproteins; Glycosylation; Host-Pathogen Interactions; Humans; Protein Processing, Post-Translational
PubMed: 34674797
DOI: 10.5483/BMBRep.2021.54.11.129 -
Cells Apr 2020Host-pathogen interactions are fundamental to our understanding of infectious diseases. Protein glycosylation is one kind of common post-translational modification,... (Review)
Review
Host-pathogen interactions are fundamental to our understanding of infectious diseases. Protein glycosylation is one kind of common post-translational modification, forming glycoproteins and modulating numerous important biological processes. It also occurs in host-pathogen interaction, affecting host resistance or pathogen virulence often because glycans regulate protein conformation, activity, and stability, etc. This review summarizes various roles of different glycoproteins during the interaction, which include: host glycoproteins prevent pathogens as barriers; pathogen glycoproteins promote pathogens to attack host proteins as weapons; pathogens glycosylate proteins of the host to enhance virulence; and hosts sense pathogen glycoproteins to induce resistance. In addition, this review also intends to summarize the roles of lectin (a class of protein entangled with glycoprotein) in host-pathogen interactions, including bacterial adhesins, viral lectins or host lectins. Although these studies show the importance of protein glycosylation in host-pathogen interaction, much remains to be discovered about the interaction mechanism.
Topics: Animals; Glycoproteins; Glycosylation; Host-Pathogen Interactions; Humans; Lectins; Polysaccharides; Protein Processing, Post-Translational
PubMed: 32326128
DOI: 10.3390/cells9041022 -
ELife Mar 2023Cancer secretome is a reservoir for aberrant glycosylation. How therapies alter this post- translational cancer hallmark and the consequences thereof remain elusive....
Cancer secretome is a reservoir for aberrant glycosylation. How therapies alter this post- translational cancer hallmark and the consequences thereof remain elusive. Here, we show that an elevated secretome fucosylation is a pan-cancer signature of both response and resistance to multiple targeted therapies. Large-scale pharmacogenomics revealed that fucosylation genes display widespread association with resistance to these therapies. In cancer cell cultures, xenograft mouse models, and patients, targeted kinase inhibitors distinctively induced core fucosylation of secreted proteins less than 60 kDa. Label-free proteomics of N-glycoproteomes identified fucosylation of the antioxidant PON1 as a critical component of the therapy-induced secretome (TIS). N-glycosylation of TIS and target core fucosylation of PON1 are mediated by the fucose salvage-FUT8-SLC35C1 axis with PON3 directly modulating GDP-Fuc transfer on PON1 scaffolds. Core fucosylation in the Golgi impacts PON1 stability and folding prior to secretion, promoting a more degradation-resistant PON1. Global and PON1-specific secretome de-N-glycosylation both limited the expansion of resistant clones in a tumor regression model. We defined the resistance-associated transcription factors (TFs) and genes modulated by the N-glycosylated TIS via a focused and transcriptome-wide analyses. These genes characterize the oxidative stress, inflammatory niche, and unfolded protein response as important factors for this modulation. Our findings demonstrate that core fucosylation is a common modification indirectly induced by targeted therapies that paradoxically promotes resistance.
Topics: Humans; Animals; Mice; Glycosylation; Secretome; Protein Processing, Post-Translational; Aryldialkylphosphatase
PubMed: 36961502
DOI: 10.7554/eLife.75191 -
Cell Death & Disease Mar 2023N-glycosylation is one of the most common types of protein modifications and it plays a vital role in normal physiological processes. However, aberrant N-glycan... (Review)
Review
N-glycosylation is one of the most common types of protein modifications and it plays a vital role in normal physiological processes. However, aberrant N-glycan modifications are closely associated with the pathogenesis of diverse diseases, including processes such as malignant transformation and tumor progression. It is known that the N-glycan conformation of the associated glycoproteins is altered during different stages of hepatocarcinogenesis. Characterizing the heterogeneity and biological functions of glycans in liver cancer patients will facilitate a deeper understanding of the molecular mechanisms of liver injury and hepatocarcinogenesis. In this article, we review the role of N-glycosylation in hepatocarcinogenesis, focusing on epithelial-mesenchymal transition, extracellular matrix changes, and tumor microenvironment formation. We highlight the role of N-glycosylation in the pathogenesis of liver cancer and its potential applications in the treatment or diagnosis of liver cancer.
Topics: Humans; Glycosylation; Glycoproteins; Liver Neoplasms; Protein Processing, Post-Translational; Polysaccharides; Tumor Microenvironment
PubMed: 36990999
DOI: 10.1038/s41419-023-05733-z -
Frontiers in Endocrinology 2023Osteoarthritis (OA) is the most common degenerative and progressive joint disease. Cellular senescence is an irreversible cell cycle arrest progressive with age, while...
Osteoarthritis (OA) is the most common degenerative and progressive joint disease. Cellular senescence is an irreversible cell cycle arrest progressive with age, while protein glycosylation is the most abundant post-translational modification, regulating various cellular and biological pathways. The implication of either chondrocyte senescence or protein glycosylation in the OA pathogenesis has been extensively and individually studied. In this study, we aimed to investigate the possible relationship between chondrocyte senescence and protein glycosylation on the pathogenesis of OA using single-cell RNA sequencing datasets of clinical OA specimens deposited in the Gene Expression Omnibus database with a different cohort. We demonstrated that both cellular senescence signal and protein glycosylation pathways in chondrocytes are validly associated with OA pathogenesis. In addition, the cellular senescence signal is well-connected to the O-linked glycosylation pathway in OA chondrocyte and vice-versa. The expression levels of the polypeptide N-acetylgalactosaminyltransferase (GALNT) family, which is essential for the biosynthesis of O-Glycans at the early stage, are highly upregulated in OA chondrocytes. Moreover, the expression levels of the GALNT family are prominently associated with chondrocyte senescence as well as pathological features of OA. Collectively, these findings uncover a crucial relationship between chondrocyte senescence and O-linked glycosylation on the OA pathophysiology, thereby revealing a potential target for OA.
Topics: Humans; Chondrocytes; Glycosylation; Osteoarthritis; Cellular Senescence; Protein Processing, Post-Translational
PubMed: 37265706
DOI: 10.3389/fendo.2023.1153689 -
Glycobiology Mar 2020Protein N- and O-glycosylation are well known co- and post-translational modifications of immunoglobulins. Antibody glycosylation on the Fab and Fc portion is known to... (Review)
Review
Protein N- and O-glycosylation are well known co- and post-translational modifications of immunoglobulins. Antibody glycosylation on the Fab and Fc portion is known to influence antigen binding and effector functions, respectively. To study associations between antibody glycosylation profiles and (patho) physiological states as well as antibody functionality, advanced technologies and methods are required. In-depth structural characterization of antibody glycosylation usually relies on the separation and tandem mass spectrometric (MS) analysis of released glycans. Protein- and site-specific information, on the other hand, may be obtained by the MS analysis of glycopeptides. With the development of high-resolution mass spectrometers, antibody glycosylation analysis at the intact or middle-up level has gained more interest, providing an integrated view of different post-translational modifications (including glycosylation). Alongside the in-depth methods, there is also great interest in robust, high-throughput techniques for routine glycosylation profiling in biopharma and clinical laboratories. With an emphasis on IgG Fc glycosylation, several highly robust separation-based techniques are employed for this purpose. In this review, we describe recent advances in MS methods, separation techniques and orthogonal approaches for the characterization of immunoglobulin glycosylation in different settings. We put emphasis on the current status and expected developments of antibody glycosylation analysis in biomedical, biopharmaceutical and clinical research.
Topics: Communicable Diseases; Glycosylation; Humans; Immunoglobulins; Polysaccharides; Tandem Mass Spectrometry
PubMed: 31281930
DOI: 10.1093/glycob/cwz048