Heparan Sulfate Containing Unsubstituted Glucosamine Residues

Nadanaka, Satomi; Purunomo, Eko; Takeda, Naoko; Tamura, Jun’ichi; Kitagawa, Hiroshi

doi:10.1074/jbc.m113.545343

Cited by 28 publications

(41 citation statements)

References 45 publications

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“…A capsular polymeric (Mw 35-49 kDa) GAG of the Escherichia coli strain K5 showed the same structure of the HS/heparin natural biosynthetic precursor N-acetyl heparosan constituted by a regular sequence of [GlcAβ1-4-GlcNAc α1-4] n [56]. This discovery was extremely useful in the search for new anticoagulant and antithrombotic heparins endowed with better pharmacokinetic and fewer side effects [53] and analogously, in the identification of non-anticoagulant congeners to be evaluated in other therapeutic fields. The progress in the knowledge of the HS/heparin biosynthetic pathway [57,58] has opened the way for chemo-enzymatic synthesis of polymers called "bioheparin" [59] and "bioengineered heparins" [60].…”

Section: Natural and Semi-synthetic Derivativesmentioning

confidence: 89%

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Non-Anticoagulant Heparins as Heparanase Inhibitors

Cassinelli

Torri

Naggi

2020

Advances in Experimental Medicine and Biology

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Section: Natural and Semi-synthetic Derivativesmentioning

confidence: 89%

“…These findings suggest a possible role of GlcNH 3 + 6S in imparting heparanase degradation resistance to HS chains in these malignant cells. Indeed, the synthetic tetrasaccharide ( [53].…”

Section: Heparanase: Discovery and Characterizationmentioning

confidence: 99%

Non-Anticoagulant Heparins as Heparanase Inhibitors

Cassinelli

Torri

Naggi

2020

Advances in Experimental Medicine and Biology

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“…Biotinylated CS-E was immobilized on a Nunc Immobilizer TM streptavidin 96-well plate (Nalge Nunc International, Rochester, NY) as described previously (56,57). Briefly, CS-E was dissolved in 100 mM MES-NaOH, pH 5.5, at a concentration of 1 mg/ml.…”

Section: Binding Assaymentioning

confidence: 99%

Chondroitin sulfate–mediated N-cadherin/β-catenin signaling is associated with basal-like breast cancer cell invasion

Nadanaka

Kinouchi

Kitagawa

2018

Journal of Biological Chemistry

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Tumor metastasis involves cancer cell invasion across basement membranes and interstitial tissues. The initial invasion step consists of adherence of the tumor cell to the extracellular matrix (ECM), and this binding transduces a variety of signals from the ECM to the tumor cell. Accordingly, it is critical to establish the mechanisms by which extracellular cues influence the intracellular activities that regulate tumor cell invasion. Here, we found that invasion of the basal-like breast cancer cell line BT-549 is enhanced by the ECM component chondroitin sulfates (CSs). CSs interacted with and induced proteolytic cleavage of N-cadherin in the BT-549 cells, yielding a C-terminal intracellular N-cadherin fragment that formed a complex with β-catenin. Of note, the cleavage of N-cadherin increased cytoplasmic and nuclear β-catenin levels; induced the matrix metalloproteinase 9 () gene, a target of β-catenin nuclear signaling; and augmented the invasion potential of the cells. We also found that CS-induced N-cadherin proteolysis requires caveolae-mediated endocytosis. An inhibitor of that process, nystatin, blocked both the endocytosis and proteolytic cleavage of N-cadherin induced by CS and also suppressed BT-549 cell invasion. Knock-out of chondroitin 4--sulfotransferase-1 (C4ST-1), a key CS biosynthetic enzyme, suppressed activation of the N-cadherin/β-catenin pathway through N-cadherin endocytosis and significantly decreased BT-549 cell invasion. These results suggest that CSs produced by C4ST-1 might be useful therapeutic targets in the management of basal-like breast cancers.

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“…For NDST one and two, the N- deacetylase reaction appears to be the limiting step for the whole NDST activity [ 155 ]. In contrast, NDST3 features a poor N- sulfotransferase activity [ 154 ], and can thus give rise to unsubstituted GlcN residue in HS, whose biological importance has been highlighted in L-selectin- or cyclophilin B dependent integrin- mediated cell adhesion, recognition [ 165 , 166 ] or heparanase inhibition [ 167 ]. Differences in domain activities, as well as potential unknown factors, lead to variability in S-domain length, which can be exacerbated by the predominance of an isoform within a tissue [ 107 ].…”

Section: Heparan Sulfate Maturationmentioning

confidence: 99%

Heparan Sulfate Proteoglycans Biosynthesis and Post Synthesis Mechanisms Combine Few Enzymes and Few Core Proteins to Generate Extensive Structural and Functional Diversity

et al. 2020

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Glycosylation is a common and widespread post-translational modification that affects a large majority of proteins. Of these, a small minority, about 20, are specifically modified by the addition of heparan sulfate, a linear polysaccharide from the glycosaminoglycan family. The resulting molecules, heparan sulfate proteoglycans, nevertheless play a fundamental role in most biological functions by interacting with a myriad of proteins. This large functional repertoire stems from the ubiquitous presence of these molecules within the tissue and a tremendous structural variety of the heparan sulfate chains, generated through both biosynthesis and post synthesis mechanisms. The present review focusses on how proteoglycans are “gagosylated” and acquire structural complexity through the concerted action of Golgi-localized biosynthesis enzymes and extracellular modifying enzymes. It examines, in particular, the possibility that these enzymes form complexes of different modes of organization, leading to the synthesis of various oligosaccharide sequences.

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Heparan Sulfate Containing Unsubstituted Glucosamine Residues

Abstract: Background:The function and biosynthetic mechanism of GlcNH 3 ϩ in heparan sulfate remain unclear.

Cited by 28 publications

References 45 publications

Non-Anticoagulant Heparins as Heparanase Inhibitors

Non-Anticoagulant Heparins as Heparanase Inhibitors

Chondroitin sulfate–mediated N-cadherin/β-catenin signaling is associated with basal-like breast cancer cell invasion

Heparan Sulfate Proteoglycans Biosynthesis and Post Synthesis Mechanisms Combine Few Enzymes and Few Core Proteins to Generate Extensive Structural and Functional Diversity

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