Identification of Chondroitin Sulfate Glucuronyltransferase as Chondroitin Synthase-3 Involved in Chondroitin Polymerization

Izumikawa, Tomomi; Koike, Toshiyasu; Shiozawa, Shoko; Sugahara, Kazuyuki; Tamura, Jun’ichi; Kitagawa, Hiroshi

doi:10.1074/jbc.m707549200

Cited by 128 publications

(73 citation statements)

References 35 publications

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“…Chondroitin sulfate assembly involves chondroitin synthase (CHSY)1, CHSY2, chondroitin polymerizing factor (CHPF), and chondroitin sulfate glucuronyltransferase (CSGlcA-T) (Izumikawa et al 2008). Among these four genes, only CHSY1 showed differential expression on the microarray in CLE lesions, which was validated by real-time PCR (Fig.…”

Section: Cd3+ T Cells Occur In Areas Of Dense Ha and Cs Stainingmentioning

confidence: 81%

Identification and Molecular Analysis of Glycosaminoglycans in Cutaneous Lupus Erythematosus and Dermatomyositis

Chang

Maheshwari

Werth

et al. 2011

J Histochem Cytochem.

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Glycosaminoglycans (GAGs), also known histologically as dermal mucin, accumulate in several inflammatory skin conditions. Because different GAG species have distinct immunologic effects, the authors examined two GAGs, hyaluronan (HA) and chondroitin sulfate (CS), using specific stains in cutaneous lupus erythematosus (CLE) and dermatomyositis (DM). In the dermis of one CLE subtype, tumid LE (TLE), they found only increased HA, but both HA and CS were significantly elevated in another CLE subtype, discoid LE (DLE). DM lesional dermis accumulated mainly CS but not HA. The authors then used glycomic gene expression microarrays to assess the expression of HA- and CS-related genes in CLE skin. Real-time quantitative PCR confirmed significantly increased expression of HAS2, CHSY1, and C4ST1 in the combined groups of CLE lesions ( n = 8) compared to healthy controls ( n = 4). Thus, the increase in HA in CLE presumably results from upregulation of HAS2, whereas CHSY1 and C4ST1 appear to contribute to increased CS. Based on their known immunomodulatory effects in other systems, HA and CS may thus participate in the pathophysiology of these inflammatory skin conditions.

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Section: Cd3+ T Cells Occur In Areas Of Dense Ha and Cs Stainingmentioning

confidence: 81%

Identification and Molecular Analysis of Glycosaminoglycans in Cutaneous Lupus Erythematosus and Dermatomyositis

Chang

Maheshwari

Werth

et al. 2011

J Histochem Cytochem.

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“…CSS1, CSS2, and CSS3 contain two glycosyltransferase domains, ␤-3 domain at the N-terminal region and ␤-4 domain at the C-terminal region and exhibit dual enzymatic activities of N-acetylgalactosaminyltransferase-II (GalNAcT-II) and glucuronyltransferase-II (GlcAT-II). Chondroitin sulfate glucuronyltransferase, similarly containing two glycosyltransferase domains, shows only GlcAT-I activity (12), although another report also indicated GalNAcT activity (15). Chondroitin sulfate N-acetylgalactosaminyltransferase-1 and -2 exhibit both GalNAcT-I and GalNAcT-II activities respon-sible for chain initiation and polymerization, respectively.…”

Section: Chondroitin Sulfate (Cs)mentioning

confidence: 99%

“…Because coexpression of dual enzymes has been shown necessary for CS chain polymerization (15,18), the other two enzymes may be redundant, or different pairs may exert a distinct function. In addition, co-expression of different pairs causes differences in chain length polymerized (18).…”

Section: Chondroitin Sulfate (Cs)mentioning

confidence: 99%

“…The enzymatic activities that catalyze CS initiation and polymerization processes are designated glycosyltransferase-I and -II activities, respectively (4). To date six glycosyltransferases for chondroitin synthesis have been identified: chondroitin sulfate synthase-1 (CSS1)/ chondroitin synthase-1 (ChSy-1), chondroitin sulfate synthase-2 (CSS2)/chondroitin polymerizing factor (ChPF), chondroitin sulfate synthase-3 (CSS3)/chondroitin synthase-2 (ChSy-2), chondroitin sulfate glucuronyltransferase/chondroitin synthase-3 (ChSy-3), and chondroitin N-acetylgalactosaminyltransferase-1 and -2 (11)(12)(13)(14)(15)(16)(17). All contain an N-terminal transmembrane domain; thus, they are type II-membrane proteins.…”

Section: Chondroitin Sulfate (Cs)mentioning

confidence: 99%

“…Numbered arrowheads 1.2, 1.7, and 3.3 indicate the eluted positions of chondroitin polysaccharides of known sizes (molecular size: 1200, 1700, and 3300, respectively). resident in the ER and the Golgi apparatus (15,27). Indeed, human CSS2 is localized at the intracellular membrane system (15).…”

Section: Figure 2 Quantification Of Transcription Levels By Real-timmentioning

confidence: 99%

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Chondroitin Sulfate Synthase-2/Chondroitin Polymerizing Factor Has Two Variants with Distinct Function*

Ogawa

Shionyu

Sugiura

et al. 2010

Journal of Biological Chemistry

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Chondroitin sulfate (CS) is a polysaccharide consisting of repeating disaccharide units of N-acetyl-D-galactosamine andD-glucuronic acid residues, modified with sulfated residues at various positions. To date six glycosyltransferases for chondroitin synthesis have been identified, and the complex of chondroitin sulfate synthase-1 (CSS1)/chondroitin synthase-1 (ChSy-1) and chondroitin sulfate synthase-2 (CSS2)/chondroitin polymerizing factor is assumed to play a major role in CS biosynthesis. We found an alternative splice variant of mouse CSS2 in a data base that lacks the N-terminal transmembrane domain, contrasting to the original CSS2. Here, we investigated the roles of CSS2 variants. Both the original enzyme and the splice variant, designated CSS2A and CSS2B, respectively, were expressed at different levels and ratios in tissues. Western blot analysis of cultured mouse embryonic fibroblasts confirmed that both enzymes were actually synthesized as proteins and were localized in both the endoplasmic reticulum and the Golgi apparatus. Pulldown assays revealed that either of CSS2A, CSS2B, and CSS1/ChSy-1 heterogeneously and homogeneously interacts with each other, suggesting that they form a complex of multimers. In vitro glycosyltransferase assays demonstrated a reduced glucuronyltransferase activity in CSS2B and no polymerizing activity in CSS2B co-expressed with CSS1, in contrast to CSS2A co-expressed with CSS1. Radiolabeling analysis of cultured COS-7 cells overexpressing each variant revealed that, whereas CSS2A facilitated CS biosynthesis, CSS2B inhibited it. Molecular modeling of CSS2A and CSS2B provided support for their properties. These findings, implicating regulation of CS chain polymerization by CSS2 variants, provide insight in elucidating the mechanisms of CS biosynthesis. Chondroitin sulfate (CS)2 is a linear polysaccharide consisting of repeating disaccharide units of N-acetyl-D-galactosamine (GalNAc) and D-glucuronic acid (GlcUA) residues, modified with sulfated residues at various positions (1-4). CS chains exhibit structural diversity in chain length and sulfation patterns, providing specific biological functions in cell adhesion, morphogenesis, neural network formation, and cell division (5-10).CS biosynthesis is initiated by transfer of GalNAc to the linkage region of a GlcA␤1-3Gal␤1-3Gal␤1-4Xyl tetrasaccharide primer that is attached to a serine residue of a core protein.Then chain polymerization takes place by the alternative addition of GalNAc and GlcUA residues. The enzymatic activities that catalyze CS initiation and polymerization processes are designated glycosyltransferase-I and -II activities, respectively (4). To date six glycosyltransferases for chondroitin synthesis have been identified: chondroitin sulfate synthase-1 (CSS1)/ chondroitin synthase-1 (ChSy-1), chondroitin sulfate synthase-2 (CSS2)/chondroitin polymerizing factor (ChPF), chondroitin sulfate synthase-3 (CSS3)/chondroitin synthase-2 (ChSy-2), chondroitin sulfate glucuronyltransferase/chondroitin synthase-3 (ChSy-3), ...

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Chondroitin polymerizing factor promotes breast carcinoma cell proliferation, invasion and migration and affects expression of epithelial‐mesenchymal transition‐related markers

et al. 2021

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Chondroitin polymerizing factor (CHPF) plays an important role in the development of certain malignant tumors. However, the role of CHPF in breast carcinoma (BRCA) and its underlying mechanism are still not fully elucidated. Expression profiles for CHPF in BRCA tissues were retrieved from The Cancer Genome Atlas database and used for prognostic analysis. Cell viability, invasion and migration were measured in vitro using MCF7 and MDA-MB-231 cell lines upon knockdown or over-expression of CHPF. Bioinformatic analysis showed that CHPF was substantially upregulated in BRCA tissues, and a quantitative reverse transcriptase-PCR was performed to confirm its upregulation in BRCA cells. High expression of CHPF was observed to be significantly associated with pathologic stage, metastasis and worse prognosis. We also observed that depletion of CHPF significantly inhibited cell proliferative, invasive and migratory abilities, whereas overexpression of CHPF exerted the opposite effects. Furthermore, analysis of the GEPIA database revealed that CHPF expression is positively correlated with the epithelial-mesenchymal transition-related markers vimentin, Snail, Slug and motion-related protein matrix metallopeptidase 2; these findings were confirmed via western blotting. Our data suggest that CHPF may contribute to BRCA progression by modulating epithelial-mesenchymal transition-related markers and matrix metallopeptidase 2 expression. Breast carcinoma (BRCA) is the most commonly diagnosed cancer in women and ranks the second among causes of cancer relative death in women [1]. Globally, the incidence rate of BRCA has been rising rapidly

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Identification of Chondroitin Sulfate Glucuronyltransferase as Chondroitin Synthase-3 Involved in Chondroitin Polymerization

Cited by 128 publications

References 35 publications

Identification and Molecular Analysis of Glycosaminoglycans in Cutaneous Lupus Erythematosus and Dermatomyositis

Identification and Molecular Analysis of Glycosaminoglycans in Cutaneous Lupus Erythematosus and Dermatomyositis

Chondroitin Sulfate Synthase-2/Chondroitin Polymerizing Factor Has Two Variants with Distinct Function*

Chondroitin polymerizing factor promotes breast carcinoma cell proliferation, invasion and migration and affects expression of epithelial‐mesenchymal transition‐related markers

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