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Annual Review of Pathology 2015Neoplastic transformation results in a wide variety of cellular alterations that impact the growth, survival, and general behavior of affected tissue. Although genetic... (Review)
Review
Neoplastic transformation results in a wide variety of cellular alterations that impact the growth, survival, and general behavior of affected tissue. Although genetic alterations underpin the development of neoplastic disease, epigenetic changes can exert an equally significant effect on neoplastic transformation. Among neoplasia-associated epigenetic alterations, changes in cellular glycosylation have recently received attention as a key component of neoplastic progression. Alterations in glycosylation appear to not only directly impact cell growth and survival but also facilitate tumor-induced immunomodulation and eventual metastasis. Many of these changes may support neoplastic progression, and unique alterations in tumor-associated glycosylation may also serve as a distinct feature of cancer cells and therefore provide novel diagnostic and even therapeutic targets.
Topics: Animals; Cell Transformation, Neoplastic; Epigenesis, Genetic; Glycosylation; Humans; Neoplasm Proteins; Neoplasms
PubMed: 25621663
DOI: 10.1146/annurev-pathol-012414-040438 -
Nature Reviews. Rheumatology Jan 2023Glycosylation has a profound influence on protein activity and cell biology through a variety of mechanisms, such as protein stability, receptor interactions and signal... (Review)
Review
Glycosylation has a profound influence on protein activity and cell biology through a variety of mechanisms, such as protein stability, receptor interactions and signal transduction. In many rheumatic diseases, a shift in protein glycosylation occurs, and is associated with inflammatory processes and disease progression. For example, the Fc-glycan composition on (auto)antibodies is associated with disease activity, and the presence of additional glycans in the antigen-binding domains of some autoreactive B cell receptors can affect B cell activation. In addition, changes in synovial fibroblast cell-surface glycosylation can alter the synovial microenvironment and are associated with an altered inflammatory state and disease activity in rheumatoid arthritis. The development of our understanding of the role of glycosylation of plasma proteins (particularly (auto)antibodies), cells and tissues in rheumatic pathological conditions suggests that glycosylation-based interventions could be used in the treatment of these diseases.
Topics: Humans; Glycomics; Glycosylation; Rheumatic Diseases; Arthritis, Rheumatoid
PubMed: 36418483
DOI: 10.1038/s41584-022-00867-4 -
Nature Reviews. Molecular Cell Biology Jun 2012Protein glycosylation is a ubiquitous post-translational modification found in all domains of life. Despite their significant complexity in animal systems, glycan... (Review)
Review
Protein glycosylation is a ubiquitous post-translational modification found in all domains of life. Despite their significant complexity in animal systems, glycan structures have crucial biological and physiological roles, from contributions in protein folding and quality control to involvement in a large number of biological recognition events. As a result, they impart an additional level of 'information content' to underlying polypeptide structures. Improvements in analytical methodologies for dissecting glycan structural diversity, along with recent developments in biochemical and genetic approaches for studying glycan biosynthesis and catabolism, have provided a greater understanding of the biological contributions of these complex structures in vertebrates.
Topics: Animals; Cell Membrane; Cytosol; Endoplasmic Reticulum; Glycoproteins; Glycosylation; Golgi Apparatus; Humans; Metabolism; Models, Biological; Polysaccharides; Protein Conformation; Protein Denaturation; Protein Folding; Protein Processing, Post-Translational; Proteins
PubMed: 22722607
DOI: 10.1038/nrm3383 -
Current Biology : CB Apr 2019Eichler introduces the diversity of protein glycosylations and the roles of these modifications in regulating protein function.
Eichler introduces the diversity of protein glycosylations and the roles of these modifications in regulating protein function.
Topics: Glycosylation; Proteins
PubMed: 30939300
DOI: 10.1016/j.cub.2019.01.003 -
Advances in understanding N-glycosylation structure, function, and regulation in health and disease.European Journal of Cell Biology 2021N-linked glycosylation is a post-translational modification crucial for membrane protein folding, stability and other cellular functions. Alteration of membrane protein... (Review)
Review
N-linked glycosylation is a post-translational modification crucial for membrane protein folding, stability and other cellular functions. Alteration of membrane protein N-glycans is implicated in wide range of pathological conditions including cancer metastasis, chronic inflammatory diseases, and viral pathogenesis. Even though the roles of N-glycans have been studied extensively, our knowledge of their mechanisms remains unclear due to the lack of detailed structural analysis of the N-glycome. Mapping the N-glycome landscape will open new avenues to explore disease mechanisms and identify novel therapeutic targets. This review discusses the diverse structure of N-linked glycans, the function and regulation of N-glycosylation in health and disease, and ends with a focus on recent approaches to target N-glycans in rheumatoid arthritis and cancer metastasis.
Topics: Glycosylation; Polysaccharides; Protein Processing, Post-Translational
PubMed: 34839178
DOI: 10.1016/j.ejcb.2021.151186 -
Current Opinion in Structural Biology Dec 2022
Topics: Glycosylation; Carbohydrates
PubMed: 36179500
DOI: 10.1016/j.sbi.2022.102468 -
Chemical Reviews Dec 2016Chemical tools have accelerated progress in glycoscience, reducing experimental barriers to studying protein glycosylation, the most widespread and complex form of... (Review)
Review
Chemical tools have accelerated progress in glycoscience, reducing experimental barriers to studying protein glycosylation, the most widespread and complex form of posttranslational modification. For example, chemical glycoproteomics technologies have enabled the identification of specific glycosylation sites and glycan structures that modulate protein function in a number of biological processes. This field is now entering a stage of logarithmic growth, during which chemical innovations combined with mass spectrometry advances could make it possible to fully characterize the human glycoproteome. In this review, we describe the important role that chemical glycoproteomics methods are playing in such efforts. We summarize developments in four key areas: enrichment of glycoproteins and glycopeptides from complex mixtures, emphasizing methods that exploit unique chemical properties of glycans or introduce unnatural functional groups through metabolic labeling and chemoenzymatic tagging; identification of sites of protein glycosylation; targeted glycoproteomics; and functional glycoproteomics, with a focus on probing interactions between glycoproteins and glycan-binding proteins. Our goal with this survey is to provide a foundation on which continued technological advancements can be made to promote further explorations of protein glycosylation.
Topics: Carbohydrates; Glycoproteins; Glycosylation; Humans; Jurkat Cells; Mass Spectrometry; Oxidation-Reduction; Proteomics
PubMed: 27960262
DOI: 10.1021/acs.chemrev.6b00023 -
Current Opinion in Structural Biology Aug 2022The structure and post-translational processing of the SARS-CoV-2 spike glycoprotein (S) is intimately associated with the function of the virus and of sterilising... (Review)
Review
The structure and post-translational processing of the SARS-CoV-2 spike glycoprotein (S) is intimately associated with the function of the virus and of sterilising vaccines. The surface of the S protein is extensively modified by glycans, and their biosynthesis is driven by both the wider cellular context, and importantly, the underlining protein structure and local glycan density. Comparison of virally derived S protein with both recombinantly derived and adenovirally induced proteins, reveal hotspots of protein-directed glycosylation that drive conserved glycosylation motifs. Molecular dynamics simulations revealed that, while the S surface is extensively shielded by N-glycans, it presents regions vulnerable to neutralising antibodies. Furthermore, glycans have been shown to influence the accessibility of the receptor binding domain and the binding to the cellular receptor. The emerging picture is one of unifying, principles of S protein glycosylation and an intimate role of glycosylation in immunogen structure and efficacy.
Topics: COVID-19; Glycosylation; Humans; Polysaccharides; Protein Binding; SARS-CoV-2
PubMed: 35717706
DOI: 10.1016/j.sbi.2022.102402 -
International Journal of Molecular... Feb 2014Protein glycosylation had been considered as an eccentricity of a few bacteria. However, through advances in analytical methods and genome sequencing, it is now... (Review)
Review
Protein glycosylation had been considered as an eccentricity of a few bacteria. However, through advances in analytical methods and genome sequencing, it is now established that bacteria possess both N-linked and O-linked glycosylation pathways. Both glycosylation pathways can modify multiple proteins, flagellins from Archaea and Eubacteria being one of these. Flagella O-glycosylation has been demonstrated in many polar flagellins from Gram-negative bacteria and in only the Gram-positive genera Clostridium and Listeria. Furthermore, O-glycosylation has also been demonstrated in a limited number of lateral flagellins. In this work, we revised the current advances in flagellar glycosylation from Gram-negative bacteria, focusing on the structural diversity of glycans, the O-linked pathway and the biological function of flagella glycosylation.
Topics: Bacterial Proteins; Flagella; Flagellin; Glycosylation; Gram-Negative Bacteria; Polysaccharides
PubMed: 24557579
DOI: 10.3390/ijms15022840 -
Frontiers in Immunology 2022Cancer immunotherapy, including the inhibition of immune checkpoints, improves the tumor immune microenvironment and is an effective tool for cancer therapy. More... (Review)
Review
Cancer immunotherapy, including the inhibition of immune checkpoints, improves the tumor immune microenvironment and is an effective tool for cancer therapy. More effective and alternative inhibitory targets are critical for successful immune checkpoint blockade therapy. The interaction of the immunomodulatory ligand B7 family with corresponding receptors induces or inhibits T cell responses by sending co-stimulatory and co-inhibitory signals respectively. Blocking the glycosylation of the B7 family members PD-L1, PD-L2, B7-H3, and B7-H4 inhibited the self-stability and receptor binding of these immune checkpoint proteins, leading to immunosuppression and rapid tumor progression. Therefore, regulation of glycosylation may be the "golden key" to relieve tumor immunosuppression. The exploration of a more precise glycosylation regulation mechanism and glycan structure of B7 family proteins is conducive to the discovery and clinical application of antibodies and small molecule inhibitors.
Topics: Humans; Glycosylation; Neoplasms; Immunotherapy; T-Lymphocytes; Immunomodulation; Tumor Microenvironment
PubMed: 36561746
DOI: 10.3389/fimmu.2022.1088560