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Biosynthesis and function of chondroitin sulfate
Authors:Tadahisa Mikami  Hiroshi Kitagawa
Institution:Department of Biochemistry, Kobe Pharmaceutical University, Higashinada-ku, Kobe 658-8558, Japan
Abstract:

Background

Chondroitin sulfate proteoglycans (CSPGs) are principal pericellular and extracellular components that form regulatory milieu involving numerous biological and pathophysiological phenomena. Diverse functions of CSPGs can be mainly attributed to structural variability of their polysaccharide moieties, chondroitin sulfate glycosaminoglycans (CS-GAG). Comprehensive understanding of the regulatory mechanisms for CS biosynthesis and its catabolic processes is required in order to understand those functions.

Scope of review

Here, we focus on recent advances in the study of enzymatic regulatory pathways for CS biosynthesis including successive modification/degradation, distinct CS functions, and disease phenotypes that have been revealed by perturbation of the respective enzymes in vitro and in vivo.

Major conclusions

Fine-tuned machineries for CS production/degradation are crucial for the functional expression of CS chains in developmental and pathophysiological processes.

General significance

Control of enzymes responsible for CS biosynthesis/catabolism is a potential target for therapeutic intervention for the CS-associated disorders.
Keywords:C4ST  chondroitin 4-O-sulfotransferase  C6ST  chondroitin 6-O-sulfotransferase  ChABC  chondroitinase ABC  ChGn  chondroitin GalNAc transferase  Chn  chondroitin  ChPF  chondroitin polymerizing factor  ChSy  chondroitin synthase  CS  chondroitin sulfate  D4ST  dermatan 4-O-sulfotransferase  DS  dermatan sulfate  DS-epi  GlcA C-5 epimerase (DS epimerase)  EXT  exostosin  EXTL  EXT-like  FAM  family with sequence similarity  GAG  glycosaminoglycan  Gal  galactose  GalNAc  N-acetylgalactosamine  GalNAc4S-6ST  GalNAc 4-sulfate 6-O-sulfotransferase  GalNAcT  GalNAc transferase  GalT-I  β1  4-galactosyltransferase-I  GalT-II  β1  3-galactosyltransferase-II  GlcA  glucuronic acid  GlcAT-I  β1  3-glucuronyltransferase-I  GlcAT-II  GlcA transferase-II  GlcNAc  N-acetylglucosamine  GlcNAcT  GlcNAc transferase  HA  hyaluronan  HNK-1  human natural killer-1  HS  heparan sulfate  HSV  herpes simplex virus  HYAL  mammalian hyaluronidase  PG  proteoglycan  Ser  serine  TM  thrombomodulin  UST  uronyl 2-O-sulfotransferase  Xyl  xylose  XylT  xylosyltransferase
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