Requirement of the conserved, hydrophobic C-terminus region for the activation of heparanase.
Requirement of the conserved, hydrophobic C-terminus region for the activation of heparanase.
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DOI：
10.1016/j.yexcr.2008.07.004
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发表时间：
2008-09
影响因子：
3.7
通讯作者：
N. Lai;S. Simizu;Daiki Morisaki;M. Muroi;H. Osada
中科院分区：
文献类型：
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作者：
N. Lai;S. Simizu;Daiki Morisaki;M. Muroi;H. Osada
乙酰肝素酶是一种内切-β-D-葡萄糖醛酸酶，负责切割硫酸乙酰肝素，参与细胞外基质降解和重塑。乙酰肝素酶活性与大量肿瘤衍生细胞类型中的转移和血管生成潜力密切相关，直接暗示乙酰肝素酶参与肿瘤进展。在这里，我们提供的第一个证据表明，疏水性的乙酰肝素酶的C-末端区域在细胞内运输，分泌，激活和乙酰肝素酶介导的肿瘤细胞迁移具有特定的作用。此外，该疏水性C-末端区域的部分缺失、疏水性C-末端区域内的亲水性氨基酸的取代以及单个氨基酸突变的实验进一步指出了疏水性C-末端区域的重要性。因此，我们的研究结果表明，乙酰肝素酶的疏水性C-末端区域是其细胞内运输到高尔基体，然后分泌，激活和肿瘤细胞迁移的决定因素。
Heparanase is an endo-β-d-glucuronidase responsible for the cleavage of heparan sulfate, participating in extracellular matrix degradation and remodeling. Heparanase activity is well correlated with the potential for metastasis and angiogenesis in a large number of tumor-derived cell types, directly implicating the involvement of heparanase in tumor progression. Here, we provide the first evidence that the hydrophobic C-terminus region of heparanase has specific roles in intracellular trafficking, secretion, activation, and heparanase-mediated tumor cell migration. Furthermore, partial deletion of this hydrophobic C-terminus region, substitution within the hydrophobic C-terminus region to hydrophilic amino acids, and experiments of single amino acid mutations further point out the importance of the hydrophobic C-terminus region. Therefore, our findings suggest that the hydrophobic C-terminus region of heparanase is a determinant for its intracellular trafficking to the Golgi apparatus, followed by secretion, activation, and tumor cell migration.