The generation of endostatin is mediated by elastase.
The generation of endostatin is mediated by elastase.
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DOI：
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发表时间：
1999-12
期刊：
影响因子：
11.2
通讯作者：
Wei Wen;M. Moses;D. Wiederschain;J. Arbiser;J. Folkman
中科院分区：
文献类型：
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作者：
Wei Wen;M. Moses;D. Wiederschain;J. Arbiser;J. Folkman
内皮抑素是一种有效的血管生成和肿瘤生长抑制剂，是胶原蛋白 XVIII 的 COOH 末端片段，是通过一种尚未鉴定的内皮抑素加工酶裂解丙氨酸-组氨酸键而衍生的。内皮抑素最初是从血管内皮瘤 (EOMA) 细胞的条件培养基中分离出来的。通过研究 EOMA 细胞将 XVIII 胶原蛋白加工成内皮抑素，我们在此表明内皮抑素的生成可以由弹性蛋白酶活性介导。我们还表明，弹性蛋白酶家族的几个成员可以通过特异性裂解丙氨酸-组氨酸键并从前体分子中释放内皮抑素来充当内皮抑素加工酶。我们进一步表明，从胶原蛋白 XVIII 生成内皮抑素至少是一个两步过程，涉及金属依赖性的早期步骤和弹性蛋白酶活性依赖性的最终步骤。
Endostatin, a potent inhibitor of angiogenesis and tumor growth, is a COOH-terminal fragment of collagen XVIII derived through cleavage of an Ala-His linkage by an as yet unidentified endostatin-processing enzyme. Endostatin was originally isolated from the conditioned medium of hemangioendothelioma (EOMA) cells. By investigating the processing of collagen XVIII to endostatin by EOMA cells, we show here that the generation of endostatin can be mediated by an elastase activity. We also show that several members of the elastase family can act as an endostatin-processing enzyme by specifically cleaving the Ala-His linkage and releasing endostatin from a precursor molecule. We further suggest that the generation of endostatin from collagen XVIII is at least a two-step process, involving a metal-dependent early step and an elastase activity-dependent final step.