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Chondroitin Polymerizing Factor, Chondroitin Polymerizing Factor 2, Chondroitin Sulfate Synthase 1,3 (CHPF, CHPF2, CHSY1, CHSY3)

  • Hiroshi Kitagawa
  • Satomi Nadanaka
Reference work entry

Abstract

Chondroitin sulfate (CS) biosynthesis is initiated by the addition of xylose to serine residues in a core protein, followed by the sequential addition of two Gal residues and a GlcA residue to form the tetrasaccharide linkage structure GlcAβ1-3Galβ1-3Galβ1-4Xylβ1-O-Ser. Chondroitin polymerization with alternating GalNAc and GlcA then takes place, forming the repeating disaccharide region. Although the repeating disaccharide region is biosynthesized by GlcA transferase II (GlcAT-II) and GalNAc transferase II (GalNAcT-II), cDNA cloning of these enzymes had not been achieved previously, because of the difficulty in purifying the enzymes to homogeneity. This prompted Kitagawa et al. to identify a human chondroitin synthase, CHSY1, from the HUGE (Human Unidentified Gene-Encoded large proteins) protein database by screening using two keywords, “one transmembrane domain” and “galactosyltransferase family” (Kitagawa et al. 2001), and the genes involved in CS biosynthesis were cloned one after another. Until now, almost the all genes involved in biosynthesis of CS have been cloned, and extensive biochemical analyses have been carried out to characterize each of the CS biosynthetic enzyme proteins. Four genes, CHPF, CHPF2, CHSY1, and CHSY3, were identified as the genes engaged in chondroitin polymerization. These gene products form complexes in various combinations and exert dual GlcAT-II and GalNAcT-II activity, which plays a critical role in the biosynthesis of CS. It is suggested that each combination of the four enzyme proteins, CHPF, CHPF2, CHSY1, and CHSY3, is able to control the CS biosynthesis, since the chain length of chondroitin formed by the co-expressed enzyme proteins in multiple combinations is different. Since two groups discovered a novel function of chondroitin in embryonic cytokinesis and cell division of Caenorhabditis elegans by RNA-mediated interference and deletion mutagenesis of a chondroitin synthase homologue (Hwang et al. 2003; Mizuguchi et al. 2003), many researchers have become increasingly aware of the importance of the biological functions of CS. Most recently, the association between human diseases and the CHPF, CHPF2, CHSY1, and CHSY3 genes has been reported; the expression levels of chondroitin-synthesizing enzymes are significantly increased in colorectal cancer, and mutations in CHSY1are the cause of Temtamy preaxial brachydactyly syndrome (Li et al. 2010; Tian et al. 2010). This section will summarize the findings of a recently completed study of the molecular cloning and characterization of chondroitin polymerase family and mention the biological significances of CHPF, CHPF2, CHSY1, and CHSY3.

Keywords

Notch Signaling Chondroitin Sulfate Myeloma Cell Bone Morphogenetic Protein Signaling Acceptor Substrate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Japan 2014

Authors and Affiliations

  1. 1.Department of BiochemistryKobe Pharmaceutical UniversityHigashinada-kuJapan

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