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Advances in Experimental Medicine and... 2021Although changes in protein glycosylation are observed in a wide range of diseases and pathological states, the examples of use of glycans as biomarkers and therapeutic... (Review)
Review
Although changes in protein glycosylation are observed in a wide range of diseases and pathological states, the examples of use of glycans as biomarkers and therapeutic targets are limited. This is not in small part because the understanding of human glycome regulation in vivo is incomplete and fragmented. Combination of human glycomics and genomics offers a powerful "data-driven hypotheses" approach to dissect the complex human glycobiology in vivo in an agnostic manner.In this chapter we review a decade of quantitative genetic studies of human N-glycome, including studies of its heritability and gene-mapping via genome-wide association studies (GWASs). We show that GWASs of human N-glycome start revealing regulators of the biochemical network of N-glycosylation. Some of these regulators demonstrate pleiotropic effects on human disease, especially autoimmune and inflammatory. We emphasize the use of in silico functional methods and multi-omics approaches to prioritize functional mechanisms to be further validated in laboratory experiments. This combined approach will lead to better understanding of mechanisms of regulation of human protein glycosylation and will provide a rich source of etiologic insight, therapeutic interventions, and biomarkers.
Topics: Genome-Wide Association Study; Genomics; Glycomics; Glycosylation; Humans; Polysaccharides
PubMed: 34495534
DOI: 10.1007/978-3-030-70115-4_7 -
Glycoconjugate Journal Jun 2023After tissue damage, a series of molecular and cellular events are initiated to promote tissue repair and regeneration to restore its original structure and function.... (Review)
Review
After tissue damage, a series of molecular and cellular events are initiated to promote tissue repair and regeneration to restore its original structure and function. These events include inter-cell communication, cell proliferation, cell migration, extracellular matrix differentiation, and other critical biological processes. Glycosylation is the crucial conservative and universal post-translational modification in all eukaryotic cells [1], with influential roles in intercellular recognition, regulation, signaling, immune response, cellular transformation, and disease development. Studies have shown that abnormally glycosylation of proteins is a well-recognized feature of cancer cells, and specific glycan structures are considered markers of tumor development. There are many studies on gene expression and regulation during tissue repair and regeneration. Still, there needs to be more knowledge of complex carbohydrates' effects on tissue repair and regeneration, such as glycosylation. Here, we present a review of studies investigating protein glycosylation in the tissue repair and regeneration process.
Topics: Glycosylation; Wound Healing; Carbohydrates; Polysaccharides; Protein Processing, Post-Translational
PubMed: 37097318
DOI: 10.1007/s10719-023-10117-8 -
Klinicka Onkologie : Casopis Ceske a... 2022Glycosylation is a posttranslational modification responsible for many bio-logical processes including protein-protein interactions, cell signaling or cell cycle... (Review)
Review
BACKGROUND
Glycosylation is a posttranslational modification responsible for many bio-logical processes including protein-protein interactions, cell signaling or cell cycle regulation. Changes in glycosylation of serum proteins reflects the status of tissues and cells in the organism and therefore can be used as markers for dia-gnosis of cancer, its progression and determination of its subtypes. N-glycan profiling is often used for characterization of N-glycosylation changes. It is based on the measurements of N-glycans released from the serum proteins. Beside the N-glycan profiling, glycoproteomic approach is emerging as it preserves the information about glycan composition, original protein, and its glycosylation sites.
PURPOSE
This review covers existing works describing the changes in serum protein N-glycosylation in various cancer types. Attention was paid to both the glycomic and glycoproteomic approaches. The last part of the review shortly presents the analytical methods used for these analyses.
Topics: Blood Proteins; Glycomics; Glycosylation; Humans; Neoplasms; Polysaccharides
PubMed: 35760569
DOI: 10.48095/ccko2022174 -
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 -
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 -
Advances in Experimental Medicine and... 2021O-Linked glycosylation such as O-fucose, O-glucose, and O-N-acetylglucosamine are considered to be unusual. As suggested by the high levels of evolutional conservation,...
O-Linked glycosylation such as O-fucose, O-glucose, and O-N-acetylglucosamine are considered to be unusual. As suggested by the high levels of evolutional conservation, these O-glycans are fundamentally important for life. In the last two decades, our understanding of the importance of these glycans has greatly advanced. In particular, identification of the glycosyltransferases responsible for the biosynthesis of these glycans has accelerated basic research on the functional significance and molecular mechanisms by which these O-glycans regulate protein functions as well as clinical research on human diseases due to changes in these types of O-glycosylation. Notably, Notch receptor signaling is modified with and regulated by these types of O-glycans. Here, we summarize the current view of the structures and the significance of these O-glycans mainly in the context of Notch signaling regulation and human diseases.
Topics: Fucose; Glucose; Glycosylation; Humans; Polysaccharides; Receptors, Notch; Signal Transduction
PubMed: 34495532
DOI: 10.1007/978-3-030-70115-4_5 -
Biology of Reproduction Dec 2023Infertility is a challenging health problem that affects 8-15% of couples worldwide. Establishing pregnancy requires successful embryo implantation, but about 85% of... (Review)
Review
Infertility is a challenging health problem that affects 8-15% of couples worldwide. Establishing pregnancy requires successful embryo implantation, but about 85% of unsuccessful pregnancies are due to embryo implantation failure or loss soon after. Factors crucial for successful implantation include invasive blastocysts, receptive endometrium, invasion of trophoblast cells, and regulation of immune tolerance at the maternal-fetal interface. Maternal-fetal crosstalk, which relies heavily on protein-protein interactions, is a critical factor in implantation that involves multiple cellular communication and molecular pathways. Glycosylation, a protein modification process, is closely related to cell growth, adhesion, transport, signal transduction, and recognition. Protein glycosylation plays a crucial role in maternal-fetal crosstalk and can be divided into N-glycosylation and O-glycosylation, which are often terminated by sialylation or fucosylation. This review article examines the role of protein glycosylation in maternal-fetal crosstalk based on two transcriptome datasets from the GEO database (GSE139087 and GSE113790) and existing research, particularly in the context of the mechanism of protein glycosylation and embryo implantation. Dysregulation of protein glycosylation can lead to adverse pregnancy outcomes, such as missed abortion and recurrent spontaneous abortion, underscoring the importance of a thorough understanding of protein glycosylation in the diagnosis and treatment of female reproductive disorders. This knowledge could have significant clinical implications, leading to the development of more effective diagnostic and therapeutic approaches for these conditions.
Topics: Pregnancy; Female; Humans; Glycosylation; Embryo Implantation; Endometrium; Pregnancy Outcome; Abortion, Habitual
PubMed: 37658761
DOI: 10.1093/biolre/ioad105 -
Advances in Protein Chemistry and... 2020Glycosylation is one of the most important modifications of proteins and lipids, and cell surface glycoconjugates are thought to play important roles in a variety of... (Review)
Review
Glycosylation is one of the most important modifications of proteins and lipids, and cell surface glycoconjugates are thought to play important roles in a variety of biological functions including cell-cell and cell-substrate interactions, bacterial adhesion, cell immunogenicity and cell signaling. Alterations of glycosylation are observed in a number of inflammatory diseases. Pro-inflammatory cytokines have been shown to modulate cell surface glycosylation by regulating the expression of glycosyltransferases and sulfotransferases involved in the biosynthesis of glycan chains, inducing the expression of specific carbohydrate antigens at the cell surface that can be recognized by different types of lectins or by bacterial adhesins, contributing to the development of diseases. Glycosylation can also regulate biological functions of immune cells by recruiting leukocytes to inflammation sites with pro- or anti-inflammatory effects. Cell surface proteoglycans provide a large panel of binding sites for many mediators of inflammation, and regulate their bio-availability and functions. In this review, we summarize the current knowledge of the glycosylation changes occurring in mucin type O-linked glycans, glycosaminoglycans, as well as in glycosphingolipids, with a particular focus on cystic fibrosis and neurodegenerative diseases, and their consequences on cell interactions and disease progression.
Topics: Animals; Glycosylation; Humans; Inflammation; Inflammatory Bowel Diseases; Neurodegenerative Diseases
PubMed: 31997767
DOI: 10.1016/bs.apcsb.2019.08.008 -
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