Nadanaka Satomi, Kitagawa Hiroshi
Department of Biochemistry, Kobe Pharmaceutical University, Kobe 658-8558, Japan.
J Biochem. 2008 Jul;144(1):7-14. doi: 10.1093/jb/mvn040. Epub 2008 Mar 26.
Proteoglycans carrying heparan sulphate (HS) chains are ubiquitously expressed at cell surfaces and in extra-cellular matrices, and HS chains interact with numerous proteins, including growth factors, morphogens and extra-cellular-matrix proteins. These interactions form the basis of HS-related biological phenomena. Thus, the biosynthesis of HS regulates key events in embryonic development and homeostasis, and deranged HS biosynthesis could cause diseases. EXT1 and EXT2 genes encoding the polymerase responsible for HS biosynthesis are known as causative genes of hereditary multiple exostoses, a dominantly inherited genetic disorder characterized by the formation of multiple cartilaginous tumours. In this review, we will summarize HS biosynthesis in several model animals, the effects on cellular functions by alteration of HS biosynthesis, and HS-associated diseases. This review suggests that HS biosynthetic enzymes would be potential candidates for drug targets in various diseases.
携带硫酸乙酰肝素（HS）链的蛋白聚糖在细胞表面和细胞外基质中广泛表达，并且HS链与众多蛋白质相互作用，包括生长因子、形态发生素和细胞外基质蛋白。这些相互作用构成了与HS相关的生物学现象的基础。因此，HS的生物合成调节胚胎发育和体内平衡中的关键事件，而HS生物合成紊乱可能导致疾病。编码负责HS生物合成的聚合酶的EXT1和EXT2基因是遗传性多发性骨软骨瘤的致病基因，这是一种以形成多个软骨肿瘤为特征的显性遗传疾病。在本综述中，我们将总结几种模式动物中的HS生物合成、HS生物合成改变对细胞功能的影响以及与HS相关的疾病。本综述表明，HS生物合成酶可能是各种疾病药物靶点的潜在候选者。
