Vreys Veronique, David Guido
Department of Molecular and Developmental Genetics, VIB, Leuven, Belgium.
J Cell Mol Med. 2007 May-Jun;11(3):427-52. doi: 10.1111/j.1582-4934.2007.00039.x.
Heparan sulphate proteoglycans are ubiquitous macromolecules of cell surfaces and extracellular matrices. Numerous extracellular matrix proteins, growth factors, morphogens, cytokines, chemokines and coagulation factors are bound and regulated by heparan sulphate. Degradation of heparan sulphate thus potentially profoundly affects cell and tissue function. Although there is evidence that several heparan sulphate-degrading endoglucuronidases (heparanases) might exist, so far only one transcript encoding a functional heparanase has been identified: heparanase-1. In the first part of this review, we discuss the current knowledge about heparan sulphate proteoglycans and the functional importance of their versatile interactions. In the second part, we summarize recent findings that have contributed to the characterization of heparanase-1, focusing on the molecular properties, working mechanism, substrate specificity, expression pattern, cellular activation and localization of this enzyme. Additionally, we review data implicating heparanase-1 in several normal and pathological processes, focusing on tumour metastasis and angiogenesis, and on evidence for a potentially direct signalling function of the molecule. In that context, we also briefly discuss heparanase-2, an intriguing close homologue of heparanase-1, for which, so far, no heparan sulphate-degrading activity could be demonstrated.
硫酸乙酰肝素蛋白聚糖是细胞表面和细胞外基质中普遍存在的大分子。许多细胞外基质蛋白、生长因子、形态发生素、细胞因子、趋化因子和凝血因子都与硫酸乙酰肝素结合并受其调节。因此，硫酸乙酰肝素的降解可能会对细胞和组织功能产生深远影响。尽管有证据表明可能存在几种降解硫酸乙酰肝素的内切葡糖醛酸酶（乙酰肝素酶），但到目前为止，仅鉴定出一种编码功能性乙酰肝素酶的转录本：乙酰肝素酶-1。在本综述的第一部分，我们讨论了关于硫酸乙酰肝素蛋白聚糖的现有知识及其多样相互作用的功能重要性。在第二部分中，我们总结了有助于乙酰肝素酶-1特性描述的最新发现，重点关注该酶的分子特性、作用机制、底物特异性、表达模式、细胞激活和定位。此外，我们回顾了表明乙酰肝素酶-1参与多种正常和病理过程的数据，重点关注肿瘤转移和血管生成，以及该分子潜在直接信号功能的证据。在此背景下，我们还简要讨论了乙酰肝素酶-2，它是乙酰肝素酶-1有趣的紧密同源物，目前尚未证明其具有硫酸乙酰肝素降解活性。
