-
Histochemistry and Cell Biology Feb 2017Proteins undergo co- and posttranslational modifications, and their glycosylation is the most frequent and structurally variegated type. Histochemically, the detection... (Review)
Review
Proteins undergo co- and posttranslational modifications, and their glycosylation is the most frequent and structurally variegated type. Histochemically, the detection of glycan presence has first been performed by stains. The availability of carbohydrate-specific tools (lectins, monoclonal antibodies) has revolutionized glycophenotyping, allowing monitoring of distinct structures. The different types of protein glycosylation in Eukaryotes are described. Following this educational survey, examples where known biological function is related to the glycan structures carried by proteins are given. In particular, mucins and their glycosylation patterns are considered as instructive proof-of-principle case. The tissue and cellular location of glycoprotein biosynthesis and metabolism is reviewed, with attention to new findings in goblet cells. Finally, protein glycosylation in disease is documented, with selected examples, where aberrant glycan expression impacts on normal function to let disease pathology become manifest. The histological applications adopted in these studies are emphasized throughout the text.
Topics: Cell Biology; Colon; Eukaryota; Glycosylation; Goblet Cells; Humans; Models, Molecular; Polysaccharides; Proteins
PubMed: 28012131
DOI: 10.1007/s00418-016-1526-4 -
Seminars in Cancer Biology Jun 2017Although altered glycosylation has been detected in human cancer cells decades ago, only investigations in the last years have enormously increased our knowledge about... (Review)
Review
Although altered glycosylation has been detected in human cancer cells decades ago, only investigations in the last years have enormously increased our knowledge about the details of protein glycosylation and its role in tumour progression. Many proteins, which are heavily glycosylated, i.e. adhesion proteins or proteases, play an important role in cancer metastasis that represents the crucial and frequently life-threatening step in progression of most tumour types. Compared to normal tissue, tumour cells often show altered glycosylation patters with appearance of new tumour-specific antigens. In this review, we give an overview about the role of glycosylation in tumour metastasis, describing recent results about O-glycans, N-glycans and glycosaminoglycans. We show that glycan structures, glycosylated proteins and glycosylation enzymes have influence on different steps of the metastatic process, including epithelial-mesenchymal transition (EMT), migration, invasion/intravasation and extravasation of tumour cells. Regarding the important role of cancer metastasis for patients survival, further knowledge about the consequences of altered glycosylation patterns in tumour cells is needed which might eventually lead to the development of novel therapeutic approaches.
Topics: Disease Progression; Epithelial-Mesenchymal Transition; Gene Expression Regulation, Neoplastic; Glycosylation; Humans; Neoplasm Metastasis; Neoplasm Proteins; Neoplasms; Protein Processing, Post-Translational
PubMed: 28315783
DOI: 10.1016/j.semcancer.2017.03.002 -
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 -
Gastroenterology Jan 2020Glycans are sequences of carbohydrates that are added to proteins or lipids to modulate their structure and function. Glycans modify proteins required for regulation of... (Review)
Review
Glycans are sequences of carbohydrates that are added to proteins or lipids to modulate their structure and function. Glycans modify proteins required for regulation of immune cells, and alterations have been associated with inflammatory conditions. For example, specific glycans regulate T-cell activation, structures, and functions of immunoglobulins; interactions between microbes and immune and epithelial cells; and malignant transformation in the intestine and liver. We review the effects of protein glycosylation in regulation of gastrointestinal and liver functions, and how alterations in glycosylation serve as diagnostic or prognostic factors, or as targets for therapy.
Topics: Biomarkers; Gastrointestinal Diseases; Gastrointestinal Tract; Glycomics; Glycosylation; Humans; Liver; Liver Diseases; Polysaccharides; Prognosis; Proteomics; T-Lymphocytes; Time Factors
PubMed: 31626754
DOI: 10.1053/j.gastro.2019.08.060 -
Trends in Molecular Medicine Apr 2022The importance of glycosylation (post-translational attachment of glycan residues to proteins) in the context of neuroinflammation is only now beginning to be... (Review)
Review
The importance of glycosylation (post-translational attachment of glycan residues to proteins) in the context of neuroinflammation is only now beginning to be understood. Although the glycome is challenging to investigate due to its complexity, this field is gaining interest because of the emergence of novel analytical methods. These investigations offer the possibility of further understanding the molecular signature of disorders with underlying neuroinflammatory cascades. In this review, we portray the clinically relevant trends in glyconeurobiology and suggest glyco-related paths that could be targeted therapeutically to decrease neuroinflammation. A combinatorial insight from glycobiology and neurology can be harnessed to better understand neuroinflammatory-related conditions to identify relevant molecular targets.
Topics: Glycosylation; Humans; Neuroinflammatory Diseases; Polysaccharides; Protein Processing, Post-Translational
PubMed: 35120836
DOI: 10.1016/j.molmed.2022.01.004 -
Biochemistry Jan 2018Protein glycosylation is one of the most common post-translational modifications and can influence many properties of proteins. Abnormal protein glycosylation can lead... (Review)
Review
Protein glycosylation is one of the most common post-translational modifications and can influence many properties of proteins. Abnormal protein glycosylation can lead to protein malfunction and serious disease. While appreciation of glycosylation's importance is growing in the scientific community, especially in recent years, a lack of homogeneous glycoproteins with well-defined glycan structures has made it difficult to understand the correlation between the structure of glycoproteins and their properties at a quantitative level. This has been a significant limitation on rational applications of glycosylation and on optimizing glycoprotein properties. Through the extraordinary efforts of chemists, it is now feasible to use chemical synthesis to produce collections of homogeneous glycoforms with systematic variations in amino acid sequence, glycosidic linkage, anomeric configuration, and glycan structure. Such a technical advance has greatly facilitated the study and application of protein glycosylation. This Perspective highlights some representative work in this research area, with the goal of inspiring and encouraging more scientists to pursue the glycosciences.
Topics: Amino Acid Sequence; Forecasting; Glycopeptides; Glycoproteins; Glycosylation; Humans; Hydrophobic and Hydrophilic Interactions; Models, Molecular; Mutagenesis, Site-Directed; Polysaccharides; Protein Conformation; Protein Engineering; Protein Processing, Post-Translational; Protein Stability
PubMed: 29309128
DOI: 10.1021/acs.biochem.7b01055 -
Nature Methods Jan 2019
Topics: Animals; Glycosylation; Nucleic Acid Hybridization; Zebrafish
PubMed: 30573827
DOI: 10.1038/s41592-018-0284-8 -
Trends in Microbiology Aug 2017Long-held to be a post-translational modification unique to Eukarya, it is now clear that both Bacteria and Archaea also perform protein glycosylation, namely the... (Review)
Review
Long-held to be a post-translational modification unique to Eukarya, it is now clear that both Bacteria and Archaea also perform protein glycosylation, namely the covalent attachment of mono- to polysaccharides to specific protein targets. At the same time, many of the roles assigned to this protein-processing event in eukaryotes, such as guiding protein folding/quality control, intracellular trafficking, dictating cellular recognition events and others, do not apply or are even irrelevant to prokaryotes. As such, protein glycosylation must serve novel functions in Bacteria and Archaea. Recent efforts have begun to elucidate some of these prokaryote-specific roles, which are addressed in this review.
Topics: Archaea; Archaeal Proteins; Bacteria; Bacterial Proteins; Glycosylation; Protein Processing, Post-Translational
PubMed: 28341406
DOI: 10.1016/j.tim.2017.03.001 -
Current Opinion in Structural Biology Jun 2019Bacterial protein glycosylation (BPG) comes in all variations of form and manifestation: N-versus O-linked, dedicated versus broad-spectrum, sequential versus en bloc... (Review)
Review
Bacterial protein glycosylation (BPG) comes in all variations of form and manifestation: N-versus O-linked, dedicated versus broad-spectrum, sequential versus en bloc glycan addition, cytoplasmic versus extracytoplasmic. Here, I evaluate and address recent advances in the field of O-linked BPG focusing on selected systems of notoriety and in which significant advances have occurred of late.
Topics: Bacteria; Bacterial Proteins; Flagellin; Glycosylation; Hexosyltransferases; Membrane Proteins; Oxygen
PubMed: 31078896
DOI: 10.1016/j.sbi.2019.03.020 -
Journal of Hematology & Oncology Sep 2016Glycosylation is the most complex post-translational modification of proteins. Altered glycans on the tumor- and host-cell surface and in the tumor microenvironment have... (Review)
Review
Glycosylation is the most complex post-translational modification of proteins. Altered glycans on the tumor- and host-cell surface and in the tumor microenvironment have been identified to mediate critical events in cancer pathogenesis and progression. Tumor-associated glycan changes comprise increased branching of N-glycans, higher density of O-glycans, generation of truncated versions of normal counterparts, and generation of unusual forms of terminal structures arising from sialylation and fucosylation. The functional role of tumor-associated glycans (Tn, sTn, T, and sLe) is dependent on the interaction with lectins. Lectins are expressed on the surface of immune cells and endothelial cells or exist as extracellular matrix proteins and soluble adhesion molecules. Expression of tumor-associated glycans is involved in the dysregulation of glycogenes, which mainly comprise glycosyltransferases and glycosidases. Furthermore, genetic and epigenetic mechanisms on many glycogenes are associated with malignant transformation. With better understanding of all aspects of cancer-cell glycomics, many tumor-associated glycans have been utilized for diagnostic, prognostic, and therapeutic purposes. Glycan-based therapeutics has been applied to cancers from breast, lung, gastrointestinal system, melanomas, and lymphomas but rarely to neuroblastomas (NBs). The success of anti-disialoganglioside (GD2, a glycolipid antigen) antibodies sheds light on glycan-based therapies for NB and also suggests the possibility of protein glycosylation-based therapies for NB. This review summarizes our understanding of cancer glycobiology with a focus of how protein glycosylation and associated glycosyltransferases affect cellular behaviors and treatment outcome of various cancers, especially NB. Finally, we highlight potential applications of glycosylation in drug and cancer vaccine development for NB.
Topics: Glycosylation; Glycosyltransferases; Humans; Neoplasm Proteins; Neoplasms; Neuroblastoma; Polysaccharides
PubMed: 27686492
DOI: 10.1186/s13045-016-0334-6