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Biotechnology Advances Sep 2023Glycosylation-mediated post-translational modification is critical for regulating many fundamental processes like cell division, differentiation, immune response, and... (Review)
Review
Glycosylation-mediated post-translational modification is critical for regulating many fundamental processes like cell division, differentiation, immune response, and cell-to-cell interaction. Alterations in the N-linked or O-linked glycosylation pattern of regulatory proteins like transcription factors or cellular receptors lead to many diseases, including cancer. These alterations give rise to micro- and macro-heterogeneity in tumor cells. Here, we review the role of O- and N-linked glycosylation and its regulatory function in autoimmunity and aberrant glycosylation in cancer. The change in cellular glycome could result from a change in the expression of glycosidases or glycosyltransferases like N-acetyl-glucosaminyl transferase V, FUT8, ST6Gal-I, DPAGT1, etc., impact the glycosylation of target proteins leading to transformation. Moreover, the mutations in glycogenes affect glycosylation patterns on immune cells leading to other related manifestations like pro- or anti-inflammatory effects. In recent years, understanding the glycome to cancer indicates that it can be utilized for both diagnosis/prognosis as well as immunotherapy. Studies involving mass spectrometry of proteome, site- and structure-specific glycoproteomics, or transcriptomics/genomics of patient samples and cancer models revealed the importance of glycosylation homeostasis in cancer biology. The development of emerging technologies, such as the lectin microarray, has facilitated research on the structure and function of glycans and glycosylation. Newly developed devices allow for high-throughput, high-speed, and precise research on aberrant glycosylation. This paper also discusses emerging technologies and clinical applications of glycosylation.
Topics: Humans; Glycosylation; Neoplasms; Glycosyltransferases; Lectins; Immunotherapy; Polysaccharides
PubMed: 37030554
DOI: 10.1016/j.biotechadv.2023.108149 -
Viruses Jul 2022The papers published in this Special Issue include various essential steps and regulatory mechanisms involved in viral protein synthesis, protein processing,...
The papers published in this Special Issue include various essential steps and regulatory mechanisms involved in viral protein synthesis, protein processing, glycosylation, and assembly [...].
Topics: Glycosylation; Protein Processing, Post-Translational; Viral Proteins
PubMed: 36016272
DOI: 10.3390/v14081650 -
Molecules (Basel, Switzerland) Apr 2023Protein glycosylation is a general post-translational modification pathway that controls various biological functions including protein trafficking, cell adhesion, and...
Protein glycosylation is a general post-translational modification pathway that controls various biological functions including protein trafficking, cell adhesion, and protein-ligand interaction [...].
Topics: Glycosylation; Protein Processing, Post-Translational; Protein Transport; Cell Adhesion
PubMed: 37050026
DOI: 10.3390/molecules28073263 -
Frontiers in Endocrinology 2023As a metabolic disease, diabetes often leads to health complications such as heart failure, nephropathy, neurological disorders, and vision loss. Diabetic retinopathy...
INTRODUCTION
As a metabolic disease, diabetes often leads to health complications such as heart failure, nephropathy, neurological disorders, and vision loss. Diabetic retinopathy (DR) affects as many as 100 million people worldwide. The mechanism of DR is complex and known to impact both neural and vascular components in the retina. While recent advances in the field have identified major cellular signaling contributing to DR pathogenesis, little has been reported on the protein post-translational modifications (PTM) - known to define protein localization, function, and activity - in the diabetic retina overall. Protein glycosylation is the enzymatic addition of carbohydrates to proteins, which can influence many protein attributes including folding, stability, function, and subcellular localization. -linked glycosylation is the addition of sugars to an oxygen atom in amino acids with a free oxygen atom in their side chain (i.e., threonine, serine). To date, more than 100 congenital disorders of glycosylation have been described. However, no studies have identified the retinal -linked glycoproteome in health or disease. With a critical need to expedite the discovery of PTMomics in diabetic retinas, we identified both global changes in protein levels and the retinal -glycoproteome of control and diabetic mice.
METHODS
We used liquid chromatography/mass spectrometry-based proteomics and high throughput screening to identify proteins differentially expressed and proteins differentially -glycosylated in the retinas of wildtype and diabetic mice.
RESULTS
Changes in both global expression levels of proteins and proteins differentially glycosylated in the retinas of wild-type and diabetic mice have been identified. We provide evidence that diabetes shifts both global expression levels and -glycosylation of metabolic and synaptic proteins in the retina.
DISCUSSION
Here we report changes in the retinal proteome of diabetic mice. We highlight alterations in global proteins involved in metabolic processes, maintaining cellular structure, trafficking, and neuronal processes. We then showed changes in -linked glycosylation of individual proteins in the diabetic retina.
Topics: Animals; Mice; Diabetes Mellitus, Experimental; Proteomics; Diabetic Retinopathy; Retina; Glycosylation; Proteome
PubMed: 37693346
DOI: 10.3389/fendo.2023.1229089 -
Electrophoresis Dec 2018Protein glycosylation, an important PTM, plays an essential role in a wide range of biological processes such as immune response, intercellular signaling, inflammation,... (Review)
Review
Protein glycosylation, an important PTM, plays an essential role in a wide range of biological processes such as immune response, intercellular signaling, inflammation, and host-pathogen interaction. Aberrant glycosylation has been correlated with various diseases. However, studying protein glycosylation remains challenging because of low abundance, microheterogeneities of glycosylation sites, and poor ionization efficiency of glycopeptides. Therefore, the development of sensitive and accurate approaches to characterize protein glycosylation is crucial. The identification and characterization of protein glycosylation by MS is referred to as the field of glycoproteomics. Methods such as enrichment, metabolic labeling, and derivatization of glycopeptides in conjunction with different MS techniques and bioinformatics tools, have been developed to achieve an unequivocal quantitative and qualitative characterization of glycoproteins. This review summarizes the recent developments in the field of glycoproteomics over the past 6 years (2012 to 2018).
Topics: Animals; Glycopeptides; Glycoproteins; Glycosylation; Humans; Mass Spectrometry; Mice; Proteomics
PubMed: 30203847
DOI: 10.1002/elps.201800272 -
Translational Psychiatry May 2023Glycosylation, the addition of glycans or carbohydrates to proteins, lipids, or other glycans, is a complex post-translational modification that plays a crucial role in... (Review)
Review
Glycosylation, the addition of glycans or carbohydrates to proteins, lipids, or other glycans, is a complex post-translational modification that plays a crucial role in cellular function. It is estimated that at least half of all mammalian proteins undergo glycosylation, underscoring its importance in the functioning of cells. This is reflected in the fact that a significant portion of the human genome, around 2%, is devoted to encoding enzymes involved in glycosylation. Changes in glycosylation have been linked to various neurological disorders, including Alzheimer's disease, Parkinson's disease, autism spectrum disorder, and schizophrenia. Despite its widespread occurrence, the role of glycosylation in the central nervous system remains largely unknown, particularly with regard to its impact on behavioral abnormalities in brain diseases. This review focuses on examining the role of three types of glycosylation: N-glycosylation, O-glycosylation, and O-GlcNAcylation, in the manifestation of behavioral and neurological symptoms in neurodevelopmental, neurodegenerative, and neuropsychiatric disorders.
Topics: Animals; Humans; Glycosylation; Autism Spectrum Disorder; Nervous System Diseases; Proteins; Protein Processing, Post-Translational; Polysaccharides; Behavioral Symptoms; Mammals
PubMed: 37156804
DOI: 10.1038/s41398-023-02446-x -
Current Opinion in Neurobiology Feb 2022Despite being caused by a single protein, prion diseases are strikingly heterogenous. Individual prion variants, known as strains, possess distinct biochemical... (Review)
Review
Despite being caused by a single protein, prion diseases are strikingly heterogenous. Individual prion variants, known as strains, possess distinct biochemical properties, form aggregates with characteristic morphologies and preferentially seed certain brain regions, causing markedly different disease phenotypes. Strain diversity is determined by protein structure, post-translational modifications and the presence of extracellular matrix components, with single amino acid substitutions or altered protein glycosylation exerting dramatic effects. Here, we review recent advances in the study of prion strains and discuss how a deeper knowledge of the molecular origins of strain heterogeneity is providing a foundation for the development of anti-prion therapeutics.
Topics: Brain; Glycosylation; Humans; Phenotype; Prion Diseases; Prions
PubMed: 34416480
DOI: 10.1016/j.conb.2021.07.010 -
Organic & Biomolecular Chemistry Aug 2022Protein glycosylation is a key post-translational modification important to many facets of biology. Glycosylation can have critical effects on protein conformation,... (Review)
Review
Protein glycosylation is a key post-translational modification important to many facets of biology. Glycosylation can have critical effects on protein conformation, uptake and intracellular routing. In immunology, glycosylation of antigens has been shown to play a role in self/non-self distinction and the effective uptake of antigens. Improperly glycosylated proteins and peptide fragments, for instance those produced by cancerous cells, are also prime candidates for vaccine design. To study these processes, access to peptides bearing well-defined glycans is of critical importance. In this review, the key approaches towards synthetic, well-defined glycopeptides, are described, with a focus on peptides useful for and used in immunological studies. Special attention is given to the glycoconjugation approaches that have been developed in recent years, as these enable rapid synthesis of various (unnatural) glycopeptides, enabling powerful carbohydrate structure/activity studies. These techniques, combined with more traditional total synthesis and chemoenzymatic methods for the production of glycopeptides, should help unravel some of the complexities of glycobiology in the near future.
Topics: Glycomics; Glycopeptides; Glycosylation; Peptides; Polysaccharides
PubMed: 35903971
DOI: 10.1039/d2ob00829g -
ACS Chemical Neuroscience Jan 2018Protein glycosylation is a posttranslational modification that affects more than half of all known proteins. Glycans covalently bound to biomolecules modulate their... (Review)
Review
Protein glycosylation is a posttranslational modification that affects more than half of all known proteins. Glycans covalently bound to biomolecules modulate their functions by both direct interactions, such as the recognition of glycan structures by binding partners, and indirect mechanisms that contribute to the control of protein conformation, stability, and turnover. The focus of this Review is the discussion of aberrant glycosylation related to brain cancer. Altered sialylation and fucosylation of N- and O-glycans play a role in the development and progression of brain cancer. Additionally, aberrant O-glycan expression has been implicated in brain cancer. This Review also addresses the clinical potential and applications of aberrant glycosylation for the detection and treatment of brain cancer. The viable roles glycans may play in the development of brain cancer therapeutics are addressed as well as cancer-glycoproteomics and personalized medicine. Glycoprotein alterations are considered as a hallmark of cancer while high expression in body fluids represents an opportunity for cancer assessment.
Topics: Animals; Brain Neoplasms; Glycosylation; Humans; Polysaccharides
PubMed: 28982002
DOI: 10.1021/acschemneuro.7b00271 -
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