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Frontiers in Immunology 2023Post-translational modification (PTM) refers to the covalent attachment of functional groups to protein substrates, resulting in structural and functional changes. PTMs... (Review)
Review
Post-translational modification (PTM) refers to the covalent attachment of functional groups to protein substrates, resulting in structural and functional changes. PTMs not only regulate the development and progression of liver cancer, but also play a crucial role in the immune response against cancer. Cancer immunity encompasses the combined efforts of innate and adaptive immune surveillance against tumor antigens, tumor cells, and tumorigenic microenvironments. Increasing evidence suggests that immunotherapies, which harness the immune system's potential to combat cancer, can effectively improve cancer patient prognosis and prolong the survival. This review presents a comprehensive summary of the current understanding of key PTMs such as phosphorylation, ubiquitination, SUMOylation, and glycosylation in the context of immune cancer surveillance against liver cancer. Additionally, it highlights potential targets associated with these modifications to enhance the response to immunotherapies in the treatment of liver cancer.
Topics: Humans; Liver Neoplasms; Protein Processing, Post-Translational; Glycosylation; Phosphorylation; Immunologic Surveillance; Tumor Microenvironment
PubMed: 37609076
DOI: 10.3389/fimmu.2023.1230465 -
Future Microbiology Jan 2017Through advances in analytical methods to detect glycoproteins and to determine glycan structures, there have been increasing reports of protein glycosylation in... (Review)
Review
Through advances in analytical methods to detect glycoproteins and to determine glycan structures, there have been increasing reports of protein glycosylation in bacteria. In this review, we summarize the known pathways for bacterial protein glycosylation: lipid carrier-mediated 'en bloc' glycosylation; and cytoplasmic stepwise protein glycosylation. The exploitation of bacterial protein glycosylation systems, especially the 'mix and match' of three independent but similar pathways (oligosaccharyltransferase-mediated protein glycosylation, lipopolysaccharide and peptidoglycan biosynthesis) in Gram-negative bacteria for glycoengineering recombinant glycoproteins is also discussed.
Topics: Bacterial Proteins; Campylobacter jejuni; Glycosylation; Gram-Positive Bacteria; Helicobacter pylori; Hexosyltransferases; Lipopolysaccharides; Membrane Proteins; Neisseria gonorrhoeae; Neisseria meningitidis; Peptidoglycan; Polysaccharides; Protein Engineering; Recombinant Proteins
PubMed: 27689684
DOI: 10.2217/fmb-2016-0166 -
Current Opinion in Structural Biology Jun 2022Biosynthetic enzymes in the secretory pathway create distributions of glycans at each glycosite that elaborate the biophysical properties and biological functions of... (Review)
Review
Biosynthetic enzymes in the secretory pathway create distributions of glycans at each glycosite that elaborate the biophysical properties and biological functions of glycoproteins. Because the biosynthetic glycosylation reactions do not go to completion, each protein glycosite is heterogeneous with respect to glycosylation. This heterogeneity means that it is not sufficient to measure protein abundance in omics experiments. Rather, it is necessary to sample the distribution of glycosylation at each glycosite to quantify the changes that occur during biological processes. On the one hand, the use of data-dependent acquisition methods to sample glycopeptides is limited by the instrument duty cycle and the missing value problem. On the other, stepped window data-independent acquisition samples all precursors, but ion abundances are limited by duty cycle. Therefore, the ability to quantify accurately the flux in glycoprotein glycosylation that occurs during biological processes requires the exploitation of emerging mass spectrometry technologies capable of deep, comprehensive sampling and selective high confidence assignment of the complex glycopeptide mixtures. This review summarizes recent technical advances and mass spectral glycoproteomics analysis strategies and how these developments impact our ability to quantify the changes in glycosylation that occur during biological processes. We highlight specific improvements to glycopeptide characterization through activated electron dissociation, ion mobility trends and instrumentation, and efficient algorithmic approaches for glycopeptide assignment. We also discuss the emerging need for unified standards to enable interlaboratory collaborations and effective monitoring of structural changes in glycoproteins.
Topics: Glycopeptides; Glycoproteins; Glycosylation; Mass Spectrometry; Polysaccharides
PubMed: 35452871
DOI: 10.1016/j.sbi.2022.102371 -
Molecules (Basel, Switzerland) Nov 2018-Glycosylation in general has impact on a diversity of biological processes covering cellular aspects (targeted transport of glycoproteins), molecular aspects (protein...
-Glycosylation in general has impact on a diversity of biological processes covering cellular aspects (targeted transport of glycoproteins), molecular aspects (protein conformation, resistance to proteolysis), and aspects involved in cellular communication (cell-cell and cell-matrix interaction). [...].
Topics: Animals; Glycoproteins; Glycosylation; Humans; Protein Processing, Post-Translational
PubMed: 30477085
DOI: 10.3390/molecules23123063 -
FEMS Microbiology Reviews Jan 2017Glycosylation of proteins is one of the most prevalent post-translational modifications occurring in nature, with a wide repertoire of biological implications. Pathways... (Review)
Review
Glycosylation of proteins is one of the most prevalent post-translational modifications occurring in nature, with a wide repertoire of biological implications. Pathways for the main types of this modification, the N- and O-glycosylation, can be found in all three domains of life-the Eukarya, Bacteria and Archaea-thereby following common principles, which are valid also for lipopolysaccharides, lipooligosaccharides and glycopolymers. Thus, studies on any glycoconjugate can unravel novel facets of the still incompletely understood fundamentals of protein N- and O-glycosylation. While it is estimated that more than two-thirds of all eukaryotic proteins would be glycosylated, no such estimate is available for prokaryotic glycoproteins, whose understanding is lagging behind, mainly due to the enormous variability of their glycan structures and variations in the underlying glycosylation processes. Combining glycan structural information with bioinformatic, genetic, biochemical and enzymatic data has opened up an avenue for in-depth analyses of glycosylation processes as a basis for glycoengineering endeavours. Here, the common themes of glycosylation are conceptualised for the major classes of prokaryotic (i.e. bacterial and archaeal) glycoconjugates, with a special focus on glycosylated cell-surface proteins. We describe the current knowledge of biosynthesis and importance of these glycoconjugates in selected pathogenic and beneficial microbes.
Topics: Archaea; Bacteria; Glycoproteins; Glycosylation; Membrane Proteins; Polysaccharides
PubMed: 27566466
DOI: 10.1093/femsre/fuw036 -
Cells Nov 2022Glycosylation is a common post-translational modification process of proteins. Mucin-type O-glycosylation is an O-glycosylation that starts from protein serine/threonine... (Review)
Review
Glycosylation is a common post-translational modification process of proteins. Mucin-type O-glycosylation is an O-glycosylation that starts from protein serine/threonine residues. Normally, it is involved in the normal development and differentiation of cells and tissues, abnormal glycosylation can lead to a variety of diseases, especially cancer. This paper reviews the normal biosynthesis of mucin-type O-glycans and their role in the maintenance of body health, followed by the mechanisms of abnormal mucin-type O-glycosylation in the development of diseases, especially tumors, including the effects of Tn, STn, T antigen, and different glycosyltransferases, with special emphasis on their role in the development of gastric cancer. Finally, tumor immunotherapy targeting mucin-type O-glycans was discussed.
Topics: Humans; Mucins; Polysaccharides; Glycosylation; Neoplasms; Glycosyltransferases; Proteins
PubMed: 36429094
DOI: 10.3390/cells11223666 -
Frontiers in Immunology 2023Protein post-translational modification (PTM) is a regulatory mechanism for protein activity modulation, localization, expression, and interactions with other cellular... (Review)
Review
Protein post-translational modification (PTM) is a regulatory mechanism for protein activity modulation, localization, expression, and interactions with other cellular molecules. It involves the addition or removal of specific chemical groups on the amino acid residues of proteins. Its common forms include phosphorylation, ubiquitylation, methylation, and acetylation. Emerging research has highlighted lactylation, succinylation, and glycosylation. PTMs are involved in vital biological processes. The occurrence and development of diseases depends on protein abundance and is regulated by various PTMs. In addition, advancements in tumor immunotherapy have revealed that protein PTM is also involved in the proliferation, activation, and metabolic reprogramming of immune cells in tumor microenvironment. These PTMs play an important role in tumor immunotherapy. In this review, we comprehensively summarize the role of several types of PTMs in tumor immunotherapy. This review could provide new insights and future research directions for tumor immunotherapy.
Topics: Humans; Neoplasms; Protein Processing, Post-Translational; Glycosylation; Phosphorylation; Immunotherapy; Tumor Microenvironment
PubMed: 37675097
DOI: 10.3389/fimmu.2023.1229397 -
Trends in Molecular Medicine Jun 2022Congenital disorders of glycosylation (CDG) are a group of more than 160 inborn errors of metabolism affecting multiple pathways of protein and lipid glycosylation.... (Review)
Review
Congenital disorders of glycosylation (CDG) are a group of more than 160 inborn errors of metabolism affecting multiple pathways of protein and lipid glycosylation. Patients present with a wide range of symptoms and therapies are only available for very few subtypes. Specific nutritional treatment options for certain CDG types include oral supplementation of monosaccharide sugars, manganese, uridine, or pyridoxine. Additional management includes specific diets (i.e., complex carbohydrate or ketogenic diet), iron supplementation, and albumin infusions. We review the dietary management in CDG with a focus on two subgroups: N-linked glycosylation defects and GPI-anchor disorders.
Topics: Congenital Disorders of Glycosylation; Glycosylation; Humans; Lipid Metabolism
PubMed: 35562242
DOI: 10.1016/j.molmed.2022.04.003 -
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