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Glycosylation and Cell Biology
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Glycosylation and Cell Biology

A topical collection in Cells (ISSN 2073-4409).

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Editor

Prof. Dr. Franz-Georg Hanisch

E-Mail Website
Collection Editor
Institute of Biochemistry II, Medical Faculty, University of Cologne, Joseph-Stelzmann-Str. 52, 50931 Köln, Germany
Interests: mucin-type O-glycosylation; O-glycoproteins; mucins; MUC1; cancer; innate immunity; galactosemia; glycomics; (glyco)proteomics; mass spectrometry
Special Issues, Collections and Topics in MDPI journals

Topical Collection Information

Dear Colleagues,

The complex interplay of sugar metabolism and protein glycosylation (evident in a series of congenital disorders) and the impact of protein dys-glycosylation on protein sorting for targeted transport and targeted protein transport to plasma membranes are currently attracting researchers’ attention. These challenging topics are related to cellular functions at higher organizational levels, such as receptor-mediated cell signaling (for example, glycosylation can be a main regulator of growth and death factor receptors’ signaling) and associated molecular pathomechanisms. A series of questions could be addressed; for instance: How is cell signaling modulated by receptor glycosylation? How is it regulated, by direct effects on protein structure (see VEGFR in endothelial cells) or by indirect effects, like altered raft sorting? What is the molecular basis of glycosylation-dependent effects on protein sorting for targeted transport to their subcellular destinations?

Another topic of high research actuality refers to rare O-glycosylation types and their regulatory influence on cellular pathways (O-GlcNAc), on cell–cell interactions (O-mannosylation of cadherins) and cell–matrix interactions, mediated by O-mannosylated lecticans in the perineural net. What is the functional implication of glycans exhibiting the protein-specific, peripheral sugar modulation LacdiNAc (e.g., in self-renewal of embryonic stem cells by regulating LIF/STAT3 signaling)?

There are many more open questions related to complex glycosylation of proteins and its functional impact at the molecular and cellular levels which could be addressed in this Topical Collection, which is designed as a platform for featuring the most recent original work on these topics together with high-standard surveys.

Prof. Franz-Georg Hanisch
Collection Editor

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Keywords

  • cell signaling
  • trafficking (targeted transport)
  • lipid rafts
  • extracellular matrix
  • glycoproteome
  • glycomics
  • N/O-glycosylation
  • rare O-glycosylation

Published Papers (13 papers)

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2024

Jump to: 2020

15 pages, 1676 KiB  
Review
Site-Specific O-glycosylation of SARS-CoV-2 Spike Protein and Its Impact on Immune and Autoimmune Responses
by Franz-Georg Hanisch
Cells 2024, 13(2), 107; https://doi.org/10.3390/cells13020107 - 5 Jan 2024
Viewed by 1957
Abstract
The world-wide COVID-19 pandemic has promoted a series of alternative vaccination strategies aiming to elicit neutralizing adaptive immunity in the human host. However, restricted efficacies of these vaccines targeting epitopes on the spike (S) protein that is involved in primary viral entry were [...] Read more.
The world-wide COVID-19 pandemic has promoted a series of alternative vaccination strategies aiming to elicit neutralizing adaptive immunity in the human host. However, restricted efficacies of these vaccines targeting epitopes on the spike (S) protein that is involved in primary viral entry were observed and putatively assigned to viral glycosylation as an effective escape mechanism. Besides the well-recognized N-glycan shield covering SARS-CoV-2 spike (S) proteins, immunization strategies may be hampered by heavy O-glycosylation and variable O-glycosites fluctuating depending on the organ sites of primary infection and those involved in immunization. A further complication associated with viral glycosylation arises from the development of autoimmune antibodies to self-carbohydrates, including O-linked blood group antigens, as structural parts of viral proteins. This outline already emphasizes the importance of viral glycosylation in general and, in particular, highlights the impact of the site-specific O-glycosylation of virions, since this modification is independent of sequons and varies strongly in dependence on cell-specific repertoires of peptidyl-N-acetylgalactosaminyltransferases with their varying site preferences and of glycan core-specific glycosyltransferases. This review summarizes the current knowledge on the viral O-glycosylation of the SARS-CoV-2 spike protein and its impact on virulence and immune modulation in the host. Full article
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2020

Jump to: 2024

18 pages, 3441 KiB  
Review
The Close Relationship between the Golgi Trafficking Machinery and Protein Glycosylation
by Anna Frappaolo, Angela Karimpour-Ghahnavieh, Stefano Sechi and Maria Grazia Giansanti
Cells 2020, 9(12), 2652; https://doi.org/10.3390/cells9122652 - 10 Dec 2020
Cited by 27 | Viewed by 5310
Abstract
Glycosylation is the most common post-translational modification of proteins; it mediates their correct folding and stability, as well as their transport through the secretory transport. Changes in N- and O-linked glycans have been associated with multiple pathological conditions including congenital disorders of [...] Read more.
Glycosylation is the most common post-translational modification of proteins; it mediates their correct folding and stability, as well as their transport through the secretory transport. Changes in N- and O-linked glycans have been associated with multiple pathological conditions including congenital disorders of glycosylation, inflammatory diseases and cancer. Glycoprotein glycosylation at the Golgi involves the coordinated action of hundreds of glycosyltransferases and glycosidases, which are maintained at the correct location through retrograde vesicle trafficking between Golgi cisternae. In this review, we describe the molecular machinery involved in vesicle trafficking and tethering at the Golgi apparatus and the effects of mutations in the context of glycan biosynthesis and human diseases. Full article
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23 pages, 6173 KiB  
Article
Desialylation of Sonic-Hedgehog by Neu2 Inhibits Its Association with Patched1 Reducing Stemness-Like Properties in Pancreatic Cancer Sphere-forming Cells
by Shalini Nath, Susmita Mondal, Ramesh Butti, Vinoth Prasanna Gunasekaran, Uttara Chatterjee, Aniket Halder, Gopal C. Kundu and Chitra Mandal
Cells 2020, 9(6), 1512; https://doi.org/10.3390/cells9061512 - 21 Jun 2020
Cited by 10 | Viewed by 3167
Abstract
Cancer stem cells (CSCs) are crucial regulators of tumor recurrence/progression. The maintenance of CSCs is dependent on aberrant activation of various pathways, including Hedgehog. Prevalent sialylations contribute to aggressiveness in CSCs. Here, we have addressed the role of sialylation in regulating stemness-like properties [...] Read more.
Cancer stem cells (CSCs) are crucial regulators of tumor recurrence/progression. The maintenance of CSCs is dependent on aberrant activation of various pathways, including Hedgehog. Prevalent sialylations contribute to aggressiveness in CSCs. Here, we have addressed the role of sialylation in regulating stemness-like properties of pancreatic cancer sphere-forming cells (PCS) through modulation of the Hedgehog (Hh) pathway. The status of CD133/CD44/surface-sialylation was checked by flow cytometry and effects of Neu2 overexpression in PCS were compared using qPCR, immunoblotting, co-immunoprecipitation and also by colony-formation assays. The work was also validated in a xenograft model after Neu2 overexpression. Neu2 and Shh status in patient tissues were examined by immunohistochemistry. PCS showed higher Hh-pathway activity and sialylation with reduced cytosolic-sialidase (Neu2). Neu2 overexpression caused desialylation of Shh, thereby reducing Shh-Patched1 binding thus causing decreased Hh-pathway activity with lower expression of Snail/Slug/CyclinD1 leading to reduction of stemness-like properties. Neu2-overexpression also induced apoptosis in PCS. Additionally, Neu2-overexpressed PCS demonstrated lower mTORC2 formation and inhibitory-phosphorylation of Gsk3β, reflecting a close relationship with reduced Hh pathway. Moreover, both Neu2 and Rictor (a major component of mTORC2) co-transfection reduced stem cell markers and Hh-pathway activity in PCS. Neu2-overexpressed tumors showed reduction in tumor mass with downregulation of stem cell markers/Shh/mTOR and upregulation of Bax/Caspase8/Caspase3. Thus, we established that reduced sialylation by Neu2 overexpression leads to decreased stemness-like properties by desialylation of Shh, which impaired its association with Patched1 thereby inhibiting the Hh pathway. All these may be responsible for enhanced apoptosis in Neu2-overexpressed PCS. Full article
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18 pages, 2567 KiB  
Article
Xylosyl Extension of O-Glucose Glycans on the Extracellular Domain of NOTCH1 and NOTCH2 Regulates Notch Cell Surface Trafficking
by Yusuke Urata, Wataru Saiki, Yohei Tsukamoto, Hiroaki Sago, Hideharu Hibi, Tetsuya Okajima and Hideyuki Takeuchi
Cells 2020, 9(5), 1220; https://doi.org/10.3390/cells9051220 - 14 May 2020
Cited by 18 | Viewed by 4342
Abstract
Biochemical and genetic studies have indicated that O-linked glycosylation such as O-glucose (Glc), fucose (Fuc), and N-acetylglucosamine (GlcNAc) is critical for Notch signaling; however, it is not fully understood how O-glycans regulate the Notch receptor function. Notch receptors are [...] Read more.
Biochemical and genetic studies have indicated that O-linked glycosylation such as O-glucose (Glc), fucose (Fuc), and N-acetylglucosamine (GlcNAc) is critical for Notch signaling; however, it is not fully understood how O-glycans regulate the Notch receptor function. Notch receptors are type-I transmembrane proteins with large extracellular domains (ECD), containing 29–36 epidermal growth factor-like (EGF) repeats. Here, we analyzed O-Glc glycans on NOTCH1 and NOTCH2 expressed in HEK293T cells using an Orbitrap Fusion mass spectrometer and successfully revealed the structures and stoichiometries of all 17 EGF repeats of NOTCH1 with the O-Glc consensus sequence (C1-X-S-X-(P/A)-C2), and 16 out of 17 EGF repeats of NOTCH2 with the same consensus sequence. High levels of O-Glc attachment and xylosyl elongation were detected on most NOTCH1 and NOTCH2 EGF repeats. When both glucoside xylosyltransferases, GXYLT1 and GXYLT2, responsible for the xylosyl elongation of O-glucose, were genetically deleted, the expression of endogenous NOTCH1 and NOTCH2 on the surface of HEK293T cells did not change, but the cell surface expression of overexpressed NOTCH1 and NOTCH2 decreased compared with that in the wild type cells. In vitro secretion assays consistently showed a reduced secretion of both the NOTCH1 and NOTCH2 ECDs in GXYLT1 and GXYLT2 double knockout cells compared with the wild type cells, suggesting a significant role of the elongation of O-Glc glycans on the Notch ECDs in the quality control of Notch receptors. Full article
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18 pages, 4085 KiB  
Article
High Expression of the Sda Synthase B4GALNT2 Associates with Good Prognosis and Attenuates Stemness in Colon Cancer
by Michela Pucci, Inês Gomes Ferreira, Martina Orlandani, Nadia Malagolini, Manuela Ferracin and Fabio Dall’Olio
Cells 2020, 9(4), 948; https://doi.org/10.3390/cells9040948 - 11 Apr 2020
Cited by 13 | Viewed by 3556
Abstract
Background: The carbohydrate antigen Sda and its biosynthetic enzyme B4GALNT2 are highly expressed in normal colonic mucosa but are down-regulated to a variable degree in colon cancer tissues. Here, we investigated the clinical and biological importance of B4GALNT2 in colon cancer. Methods: [...] Read more.
Background: The carbohydrate antigen Sda and its biosynthetic enzyme B4GALNT2 are highly expressed in normal colonic mucosa but are down-regulated to a variable degree in colon cancer tissues. Here, we investigated the clinical and biological importance of B4GALNT2 in colon cancer. Methods: Correlations of B4GALNT2 mRNA with clinical data were obtained from The Cancer Genome Atlas (TCGA) database; the phenotypic and transcriptomic changes induced by B4GALNT2 were studied in LS174T cells transfected with B4GALNT2 cDNA. Results: TCGA data indicate that patients with high B4GALNT2 expression in cancer tissues display longer survival than non-expressers. In LS174T cells, expression of B4GALNT2 did not affect the ability to heal a scratch wound or to form colonies in standard growth conditions but markedly reduced the growth in soft agar, the tridimensional (3D) growth as spheroids, and the number of cancer stem cells, indicating a specific effect of B4GALNT2 on the growth in poor adherence and stemness. On the transcriptome, B4GALNT2 induced the down-regulation of the stemness-associated gene SOX2 and modulated gene expression towards an attenuation of the cancer phenotype. Conclusions: The level of B4GALNT2 can be proposed as a marker to identify higher- and lower-risk colorectal cancer patients. Full article
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10 pages, 1727 KiB  
Article
Glycation Leads to Increased Polysialylation and Promotes the Metastatic Potential of Neuroblastoma Cells
by Maximilian Scheer, Kaya Bork, Frieder Simon, Manimozhi Nagasundaram, Rüdiger Horstkorte and Vinayaga Srinivasan Gnanapragassam
Cells 2020, 9(4), 868; https://doi.org/10.3390/cells9040868 - 2 Apr 2020
Cited by 11 | Viewed by 2783
Abstract
Neuroblastoma is the second most frequent extracranial tumor, affecting young children worldwide. One hallmark of tumors such as neuroblastomas, is the expression of polysialic acid, which interferes with adhesion and may promote invasion and metastasis. Since tumor cells use glycolysis for energy production, [...] Read more.
Neuroblastoma is the second most frequent extracranial tumor, affecting young children worldwide. One hallmark of tumors such as neuroblastomas, is the expression of polysialic acid, which interferes with adhesion and may promote invasion and metastasis. Since tumor cells use glycolysis for energy production, they thereby produce as side product methylglyoxal (MGO), which reacts with proteins to advanced glycation end products in a mechanism called glycation. Here we analyzed the expression of (poly) sialic acid and adhesion of Kelly neuroblastoma cells after glycation with MGO. We found that both sialylation and polysialylation is increased after glycation. Furthermore, glycated Kelly neuroblastoma cells had a much higher potential for migration and invasion compared with non-glycated cells. Full article
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19 pages, 21175 KiB  
Article
Characterization of Sialic Acid-Binding Immunoglobulin-Type Lectins in Fish Reveals Teleost-Specific Structures and Expression Patterns
by Kim F. Bornhöfft, Joan Martorell Ribera, Torsten Viergutz, Marzia T. Venuto, Ulrike Gimsa, Sebastian P. Galuska and Alexander Rebl
Cells 2020, 9(4), 836; https://doi.org/10.3390/cells9040836 - 31 Mar 2020
Cited by 9 | Viewed by 3525
Abstract
The cellular glycocalyx of vertebrates is frequently decorated with sialic acid residues. These sialylated structures are recognized by sialic acid-binding immunoglobulin-type lectins (Siglecs) of immune cells, which modulate their responsiveness. Fifteen Siglecs are known to be expressed in humans, but only four Siglecs [...] Read more.
The cellular glycocalyx of vertebrates is frequently decorated with sialic acid residues. These sialylated structures are recognized by sialic acid-binding immunoglobulin-type lectins (Siglecs) of immune cells, which modulate their responsiveness. Fifteen Siglecs are known to be expressed in humans, but only four Siglecs are regularly present in fish: Siglec1, CD22, myelin-associated glycoprotein (MAG), and Siglec15. While several studies have dealt with the physiological roles of these four Siglecs in mammals, little is known about Siglecs in fish. In the present manuscript, the expression landscapes of these Siglecs were determined in the two salmonid species Oncorhynchus mykiss and Coregonus maraena and in the percid fish Sander lucioperca. This gene-expression profiling revealed that the expression of MAG is not restricted to neuronal cells but is detectable in all analyzed blood cells, including erythrocytes. The teleostean MAG contains the inhibitory motif ITIM; therefore, an additional immunomodulatory function of MAG is likely to be present in fish. Besides MAG, Siglec1, CD22, and Siglec15 were also expressed in all analyzed blood cell populations. Interestingly, the expression profiles of genes encoding Siglecs and particular associated enzymes changed in a gene- and tissue-specific manner when Coregonus maraena was exposed to handling stress. Thus, the obtained data indicate once more that stress directly affects immune-associated processes. Full article
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17 pages, 4559 KiB  
Article
Immunolocalization of Keratan Sulfate in Rat Spinal Tissues Using the Keratanase Generated BKS-1(+) Neoepitope: Correlation of Expression Patterns with the Class II SLRPs, Lumican and Keratocan
by Anthony J. Hayes and James Melrose
Cells 2020, 9(4), 826; https://doi.org/10.3390/cells9040826 - 30 Mar 2020
Cited by 8 | Viewed by 3672
Abstract
This study has identified keratan sulfate in fetal and adult rat spinal cord and vertebral connective tissues using the antibody BKS-1(+) which recognizes a reducing terminal N-acetyl glucosamine-6-sulfate neo-epitope exposed by keratanase-I digestion. Labeling patterns were correlated with those of lumican and keratocan [...] Read more.
This study has identified keratan sulfate in fetal and adult rat spinal cord and vertebral connective tissues using the antibody BKS-1(+) which recognizes a reducing terminal N-acetyl glucosamine-6-sulfate neo-epitope exposed by keratanase-I digestion. Labeling patterns were correlated with those of lumican and keratocan using core protein antibodies to these small leucine rich proteoglycan species. BKS-1(+) was not immunolocalized in fetal spinal cord but was apparent in adult cord and was also prominently immunolocalized to the nucleus pulposus and inner annulus fibrosus of the intervertebral disc. Interestingly, BKS-1(+) was also strongly associated with vertebral body ossification centers of the fetal spine. Immunolocalization of lumican and keratocan was faint within the vertebral body rudiments of the fetus and did not correlate with the BKS-1(+) localization indicating that this reactivity was due to another KS-proteoglycan, possibly osteoadherin (osteomodulin) which has known roles in endochondral ossification. Western blotting of adult rat spinal cord and intervertebral discs to identify proteoglycan core protein species decorated with the BKS-1(+) motif confirmed the identity of 37 and 51 kDa BKS-1(+) positive core protein species. Lumican and keratocan contain low sulfation KS-I glycoforms which have neuroregulatory and matrix organizational properties through their growth factor and morphogen interactive profiles and ability to influence neural cell migration. Furthermore, KS has interactive capability with a diverse range of neuroregulatory proteins that promote neural proliferation and direct neural pathway development, illustrating key roles for keratocan and lumican in spinal cord development. Full article
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14 pages, 1054 KiB  
Review
O-acetylated Gangliosides as Targets for Cancer Immunotherapy
by Sumeyye Cavdarli, Philippe Delannoy and Sophie Groux-Degroote
Cells 2020, 9(3), 741; https://doi.org/10.3390/cells9030741 - 17 Mar 2020
Cited by 38 | Viewed by 5175
Abstract
O-acetylation of sialic acid residues is one of the main modifications of gangliosides, and modulates ganglioside functions. O-acetylation of gangliosides is dependent on sialyl-O-acetyltransferases and sialyl-O-acetyl-esterase activities. CAS1 Domain-Containing Protein 1 (CASD1) is the only human sialyl- [...] Read more.
O-acetylation of sialic acid residues is one of the main modifications of gangliosides, and modulates ganglioside functions. O-acetylation of gangliosides is dependent on sialyl-O-acetyltransferases and sialyl-O-acetyl-esterase activities. CAS1 Domain-Containing Protein 1 (CASD1) is the only human sialyl-O-acetyltransferases (SOAT) described until now. O-acetylated ganglioside species are mainly expressed during embryonic development and in the central nervous system in healthy adults, but are re-expressed during cancer development and are considered as markers of cancers of neuroectodermal origin. However, the specific biological roles of O-acetylated gangliosides in developing and malignant tissues have not been extensively studied, mostly because of the requirement of specific approaches and tools for sample preparation and analysis. In this review, we summarize our current knowledge of ganglioside biosynthesis and expression in normal and pathological conditions, of ganglioside O-acetylation analysis and expression in cancers, and of the possible use of O-acetylated gangliosides as targets for cancer immunotherapy. Full article
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18 pages, 4896 KiB  
Article
Fluorinated Galactoses Inhibit Galactose-1-Phosphate Uridyltransferase and Metabolically Induce Galactosemia-like Phenotypes in HEK-293 Cells
by Verena Janes, Simona Grabany, Julien Delbrouck, Stephane P. Vincent, Johannes Gottschalk, Lothar Elling and Franz-Georg Hanisch
Cells 2020, 9(3), 607; https://doi.org/10.3390/cells9030607 - 3 Mar 2020
Cited by 8 | Viewed by 4364
Abstract
Genetic defects of human galactose-1-phosphate uridyltransferase (hGALT) and the partial loss of enzyme function result in an altered galactose metabolism with serious long-term developmental impairment of organs in classic galactosemia patients. In search for cellular pathomechanisms induced by the stressor galactose, [...] Read more.
Genetic defects of human galactose-1-phosphate uridyltransferase (hGALT) and the partial loss of enzyme function result in an altered galactose metabolism with serious long-term developmental impairment of organs in classic galactosemia patients. In search for cellular pathomechanisms induced by the stressor galactose, we looked for ways to induce metabolically a galactosemia-like phenotype by hGALT inhibition in HEK293 cells. In kinetic studies, we provide evidence for 2-fluorinated galactose-1-phosphate (F-Gal-1-P) to competitively inhibit recombinant hGALT with a KI of 0.9 mM. Contrasting with hepatic cells, no alterations of N-glycoprofiles in MIG (metabolic induction of galactosemia)-HEK293 cells were revealed for an inducible secretory netrin-1 probe by MALDI-MS. Differential fluorescence-activated cell sorting demonstrated reduced surface expression of N-glycosylated CD109, EGFR, DPP4, and rhMUC1. Membrane raft proteomes exhibited dramatic alterations pointing to an affection of the unfolded protein response, and of targeted protein traffick. Most prominent, a negative regulation of oxidative stress was revealed presumably as a response to a NADPH pool depletion during reduction of Gal/F-Gal. Cellular perturbations induced by fluorinated galactoses in normal epithelial cells resemble proteomic changes revealed for galactosemic fibroblasts. In conclusion, the metabolic induction of galactosemia-like phenotypes in healthy epithelial/neuronal cells could support studies on the molecular pathomechanisms in classic galactosemia, in particular under conditions of low galactose stress and residual GALT activity. Full article
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15 pages, 2826 KiB  
Article
BGN/TLR4/NF-κB Mediates Epigenetic Silencing of Immunosuppressive Siglec Ligands in Colon Cancer Cells
by Hsiang-Chi Huang, Bi-He Cai, Ching-Shu Suen, Hsueh-Yi Lee, Ming-Jing Hwang, Fu-Tong Liu and Reiji Kannagi
Cells 2020, 9(2), 397; https://doi.org/10.3390/cells9020397 - 9 Feb 2020
Cited by 28 | Viewed by 4658
Abstract
Human Toll-like receptor (TLR) signaling plays a vital role in intestinal inflammation by activating the NF-κB pathway. By querying GENT2 datasets, we identified the gene expression level of TLR2 and TLR4 as being substantially increased in colorectal cancer. Introduction of shRNAs for TLR4 [...] Read more.
Human Toll-like receptor (TLR) signaling plays a vital role in intestinal inflammation by activating the NF-κB pathway. By querying GENT2 datasets, we identified the gene expression level of TLR2 and TLR4 as being substantially increased in colorectal cancer. Introduction of shRNAs for TLR4 but not TLR2 dramatically recovered disialyl Lewisa and sialyl 6-sulfo Lewisx glycans, which are preferentially expressed in non-malignant colonic epithelial cells and could serve as ligands for the immunosuppressive molecule Siglec-7. We screened several TLR4 ligands and found that among them BGN is highly expressed in cancers and is involved in the epigenetic silencing of Siglec-7 ligands. Suppression of BGN expression substantially downregulated NF-κB activity and the marker H3K27me3 in the promoter regions of the SLC26A2 and ST6GalNAc6 genes, which are involved in the synthesis of those glycans, and restored expression of normal glycans as well as Siglec-7 binding activities. We show that in the presence of TLR4, inflammatory stimuli initiate a positive loop involving NF-κB that activates BGN and further enhances TLR4 activity. Present findings indicate a putative mechanism for the promotion of carcinogenesis by loss of immunosuppressive ligands by the BGN/TLR4/ NF-κB pathway. Full article
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18 pages, 1652 KiB  
Review
Biological Functions and Analytical Strategies of Sialic Acids in Tumor
by Xiaoman Zhou, Ganglong Yang and Feng Guan
Cells 2020, 9(2), 273; https://doi.org/10.3390/cells9020273 - 22 Jan 2020
Cited by 104 | Viewed by 15724
Abstract
Sialic acids, a subset of nine carbon acidic sugars, often exist as the terminal sugars of glycans on either glycoproteins or glycolipids on the cell surface. Sialic acids play important roles in many physiological and pathological processes via carbohydrate-protein interactions, including cell–cell communication, [...] Read more.
Sialic acids, a subset of nine carbon acidic sugars, often exist as the terminal sugars of glycans on either glycoproteins or glycolipids on the cell surface. Sialic acids play important roles in many physiological and pathological processes via carbohydrate-protein interactions, including cell–cell communication, bacterial and viral infections. In particular, hypersialylation in tumors, as well as their roles in tumor growth and metastasis, have been widely described. Recent studies have indicated that the aberrant sialylation is a vital way for tumor cells to escape immune surveillance and keep malignance. In this article, we outline the present state of knowledge on the metabolic pathway of human sialic acids, the function of hypersialylation in tumors, as well as the recent labeling and analytical techniques for sialic acids. It is expected to offer a brief introduction of sialic acid metabolism and provide advanced analytical strategies in sialic acid studies. Full article
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19 pages, 4058 KiB  
Article
Increased O-GlcNAcylation of c-Myc Promotes Pre-B Cell Proliferation
by Da Hee Lee, Na Eun Kwon, Won-Ji Lee, Moo-Seung Lee, Doo-Jin Kim, Ji Hyung Kim and Sung-Kyun Park
Cells 2020, 9(1), 158; https://doi.org/10.3390/cells9010158 - 8 Jan 2020
Cited by 26 | Viewed by 5676
Abstract
O-linked β-N-acetylglucosamine (O-GlcNAc) modification regulates the activity of hundreds of nucleocytoplasmic proteins involved in a wide variety of cellular processes, such as gene expression, signaling, and cell growth; however, the mechanism underlying the regulation of B cell development and function by O-GlcNAcylation remains [...] Read more.
O-linked β-N-acetylglucosamine (O-GlcNAc) modification regulates the activity of hundreds of nucleocytoplasmic proteins involved in a wide variety of cellular processes, such as gene expression, signaling, and cell growth; however, the mechanism underlying the regulation of B cell development and function by O-GlcNAcylation remains largely unknown. Here, we demonstrate that changes in cellular O-GlcNAc levels significantly affected the growth of pre-B cells, which rapidly proliferate to allow expansion of functional clones that express successfully rearranged heavy chains at the pro-B stage during early B cell development. In our study, the overall O-GlcNAc levels in these proliferative pre-B cells, which are linked to the glucose uptake rate, were highly induced when compared with those in pro-B cells. Thus, pharmacologically, genetically, or nutritionally, inhibition of O-GlcNAcylation in pre-B cells markedly downregulated c-Myc expression, resulting in cell cycle arrest via blockade of cyclin expression. Importantly, the population of B cells after the pro-B cell stage in mouse bone marrow was severely impaired by the administration of an O-GlcNAc inhibitor. These results strongly suggest that O-GlcNAcylation-dependent expression of c-Myc represents a new regulatory component of pre-B cell proliferation, as well as a potential therapeutic target for the treatment of pre-B cell-derived leukemia. Full article
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