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Nature Reviews. Molecular Cell Biology Dec 2020Glycosylation is the most abundant and diverse form of post-translational modification of proteins that is common to all eukaryotic cells. Enzymatic glycosylation of... (Review)
Review
Glycosylation is the most abundant and diverse form of post-translational modification of proteins that is common to all eukaryotic cells. Enzymatic glycosylation of proteins involves a complex metabolic network and different types of glycosylation pathways that orchestrate enormous amplification of the proteome in producing diversity of proteoforms and its biological functions. The tremendous structural diversity of glycans attached to proteins poses analytical challenges that limit exploration of specific functions of glycosylation. Major advances in quantitative transcriptomics, proteomics and nuclease-based gene editing are now opening new global ways to explore protein glycosylation through analysing and targeting enzymes involved in glycosylation processes. In silico models predicting cellular glycosylation capacities and glycosylation outcomes are emerging, and refined maps of the glycosylation pathways facilitate genetic approaches to address functions of the vast glycoproteome. These approaches apply commonly available cell biology tools, and we predict that use of (single-cell) transcriptomics, genetic screens, genetic engineering of cellular glycosylation capacities and custom design of glycoprotein therapeutics are advancements that will ignite wider integration of glycosylation in general cell biology.
Topics: Carbohydrate Metabolism; Glycoproteins; Glycosylation; Humans; Metabolic Networks and Pathways; Polysaccharides; Protein Processing, Post-Translational; Proteome
PubMed: 33087899
DOI: 10.1038/s41580-020-00294-x -
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 -
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 -
Molecular Omics Oct 2020Protein glycosylation is a co- and post-translational modification that, in Leishmania parasites, plays key roles in vector-parasite-vertebrate host interaction. In the... (Review)
Review
Protein glycosylation is a co- and post-translational modification that, in Leishmania parasites, plays key roles in vector-parasite-vertebrate host interaction. In the mammalian host, Leishmania protein glycosylation is involved in virulence, host cell invasion, and immune evasion and modulation. The Leishmania glycocalyx is composed by a dense array of glycoconjugates including lipophosphoglycan, glycoinositolphospholipids, glycoproteins and proteophosphoglycans which varies in composition between Leishmania species and developmental stages. The current knowledge on Leishmania protein glycosylation is quite limited. The development of novel analytical tools to characterize the Leishmania glycoproteome and the expanding toolbox to modulate the parasite glycocode will help in deciphering the processes involved in Leishmania-host interaction. This review will recapitulate the current knowledge of Leishmania protein glycosylation, and glycan structures reported, and the potential application of mass spectrometry-based analysis for system-wide Leishmania glycoproteome and glycome analysis.
Topics: Amino Acid Sequence; Animals; Glycosylation; Humans; Leishmania; Leishmaniasis; Polysaccharides; Proteins
PubMed: 32724945
DOI: 10.1039/d0mo00043d -
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 -
Oncogene Jun 2023Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. Understanding the cancer mechanisms provides novel diagnostic, prognostic, and... (Review)
Review
Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. Understanding the cancer mechanisms provides novel diagnostic, prognostic, and therapeutic markers for the management of HCC disease. In addition to genomic and epigenomic regulation, post-translational modification exerts a profound influence on protein functions and plays a critical role in regulating various biological processes. Protein glycosylation is one of the most common and complex post-translational modifications of newly synthesized proteins and acts as an important regulatory mechanism that is implicated in fundamental molecular and cell biology processes. Recent studies in glycobiology suggest that aberrant protein glycosylation in hepatocytes contributes to the malignant transformation to HCC by modulating a wide range of pro-tumorigenic signaling pathways. The dysregulated protein glycosylation regulates cancer growth, metastasis, stemness, immune evasion, and therapy resistance, and is regarded as a hallmark of HCC. Changes in protein glycosylation could serve as potential diagnostic, prognostic, and therapeutic factors in HCC. In this review, we summarize the functional importance, molecular mechanism, and clinical application of protein glycosylation alterations in HCC.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Glycosylation; Protein Processing, Post-Translational; Carcinogenesis; Proteins
PubMed: 37193819
DOI: 10.1038/s41388-023-02702-w -
Translational Research : the Journal of... Mar 2023Human body fluids have become an indispensable resource for clinical research, diagnosis and prognosis. Urine is widely used to discover disease-specific glycoprotein... (Review)
Review
Human body fluids have become an indispensable resource for clinical research, diagnosis and prognosis. Urine is widely used to discover disease-specific glycoprotein biomarkers because of its recurrently non-invasive collection and disease-indicating properties. While urine is an unstable fluid in that its composition changes with ingested nutrients and further as it is excreted through micturition, urinary proteins are more stable and their abnormal glycosylation is associated with diseases. It is known that aberrant glycosylation can define tumor malignancy and indicate disease initiation and progression. However, a thorough and translational survey of urinary glycosylation in diseases has not been performed. In this article, we evaluate the clinical applications of urine, introduce methods for urine glycosylation analysis, and discuss urine glycoprotein biomarkers. We emphasize the importance of mining urinary glycoproteins and searching for disease-specific glycosylation in various diseases (including cancer, neurodegenerative diseases, diabetes, and viral infections). With advances in mass spectrometry-based glycomics/glycoproteomics/glycopeptidomics, characterization of disease-specific glycosylation will optimistically lead to the discovery of disease-related urinary biomarkers with better sensitivity and specificity in the near future.
Topics: Humans; Glycosylation; Glycoproteins; Protein Processing, Post-Translational; Biomarkers; Body Fluids; Neoplasms
PubMed: 35952983
DOI: 10.1016/j.trsl.2022.08.001 -
Ageing Research Reviews Aug 2023Glycosylation is a common post-translational modification of brain proteins including cell surface adhesion molecules, synaptic proteins, receptors and channels, as well... (Review)
Review
Glycosylation is a common post-translational modification of brain proteins including cell surface adhesion molecules, synaptic proteins, receptors and channels, as well as intracellular proteins, with implications in brain development and functions. Using advanced state-of-the-art glycomics and glycoproteomics technologies in conjunction with glycoinformatics resources, characteristic glycosylation profiles in brain tissues are increasingly reported in the literature and growing evidence shows deregulation of glycosylation in central nervous system disorders, including aging associated neurodegenerative diseases. Glycan signatures characteristic of brain tissue are also frequently described in cerebrospinal fluid due to its enrichment in brain-derived molecules. A detailed structural analysis of brain and cerebrospinal fluid glycans collected in publications in healthy and neurodegenerative conditions was undertaken and data was compiled to create a browsable dedicated set in the GlyConnect database of glycoproteins (https://glyconnect.expasy.org/brain). The shared molecular composition of cerebrospinal fluid with brain enhances the likelihood of novel glycobiomarker discovery for neurodegeneration, which may aid in unveiling disease mechanisms, therefore, providing with novel therapeutic targets as well as diagnostic and progression monitoring tools.
Topics: Humans; Glycosylation; Neurodegenerative Diseases; Glycoproteins; Protein Processing, Post-Translational; Glycomics; Polysaccharides; Biomarkers
PubMed: 37348818
DOI: 10.1016/j.arr.2023.101991 -
Critical Reviews in Microbiology Feb 2019Protein glycosylation systems in many bacteria are often associated with crucial biological processes like pathogenicity, immune evasion and host-pathogen interactions,... (Review)
Review
Protein glycosylation systems in many bacteria are often associated with crucial biological processes like pathogenicity, immune evasion and host-pathogen interactions, implying the significance of protein-glycan linkage. Similarly, host protein glycosylation has been implicated in antimicrobial activity as well as in promoting growth of beneficial strains. In fact, few pathogens notably modulate host glycosylation machineries to facilitate their survival. To date, diverse chemical and biological strategies have been developed for conjugate vaccine production for disease control. Bioconjugate vaccines, largely being produced by glycoengineering using PglB (the N-oligosaccharyltransferase from Campylobacter jejuni) in suitable bacterial hosts, have been highly promising with respect to their effectiveness in providing protective immunity and ease of production. Recently, a novel method of glycoconjugate vaccine production involving an O-oligosaccharyltransferase, PglL from Neisseria meningitidis, has been optimized. Nevertheless, many questions on defining antigenic determinants, glycosylation markers, species-specific differences in glycosylation machineries, etc. still remain unanswered, necessitating further exploration of the glycosylation systems of important pathogens. Hence, in this review, we will discuss the impact of bacterial protein glycosylation on its pathogenesis and the interaction of pathogens with host protein glycosylation, followed by a discussion on strategies used for bioconjugate vaccine development.
Topics: Bacteria; Bacterial Proteins; Bacterial Vaccines; Glycosylation; Host-Pathogen Interactions
PubMed: 30632429
DOI: 10.1080/1040841X.2018.1547681 -
The New Phytologist May 2021Glycosylation is a conserved set of post-translational modifications that exists in all eukaryotic cells. During the last decade, the role of glycosylation in plant... (Review)
Review
Glycosylation is a conserved set of post-translational modifications that exists in all eukaryotic cells. During the last decade, the role of glycosylation in plant pathogenic fungi has received significant attention and considerable progress has been made especially in Ustilago maydis and Magnaporthe oryzae. Here, we review recent advances in our understanding of the role of N-glycosylation, O-glycosylation and glycosylphosphatidylinositol (GPI) anchors during plant infection by pathogenic fungi. We highlight the roles of these processes in regulatory mechanisms associated with appressorium formation, host penetration, biotrophic growth and immune evasion. We argue that improved knowledge of glycosylation pathways and the impact of these modifications on fungal pathogenesis is overdue and could provide novel strategies for disease control.
Topics: Ascomycota; Basidiomycota; Fungal Proteins; Glycosylation; Magnaporthe; Oryza; Plant Diseases; Virulence
PubMed: 33454977
DOI: 10.1111/nph.17207