Secreted cysteine proteases of the carcinogenic liver fluke, Opisthorchis viverrini: regulation of cathepsin F activation by autocatalysis and trans-processing by cathepsin B.
Secreted cysteine proteases of the carcinogenic liver fluke, Opisthorchis viverrini: regulation of cathepsin F activation by autocatalysis and trans-processing by cathepsin B.
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DOI：
10.1111/j.1462-5822.2010.01433.x
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发表时间：
2010-06
影响因子：
3.4
通讯作者：
Robinson MW
中科院分区：
文献类型：
--
作者：
Sripa J;Laha T;To J;Brindley PJ;Sripa B;Kaewkes S;Dalton JP;Robinson MW
毒毛蛇是一种重要的人类寄生虫病原体，在泰国和老挝流行。成年吸虫寄生在宿主胆管内，以上皮组织和血细胞为食。慢性胆索病与严重的肝胆疾病如胆管癌有关。在这里，我们报道了成年O. viverrini分泌两种主要的半胱氨酸蛋白酶：组织蛋白酶F （Ov-CF-1）和组织蛋白酶B1 （Ov-CB-1）。Ov-CF-1是一种无活性的酶原，在pH为4.5时，通过在预节-成熟结构域交界处的分子间裂解，自动催化并激活为成熟酶。Ov-CB-1也作为酶原分泌，但与Ov-CF-1相反，尽管保留n端前段，但对肽和大分子底物具有完全活性。活性的Ov-CB-1酶原能够在pH为5.5的条件下通过蛋白水解去除其前段来反式激活Ov-CF-1，而在这个pH下Ov-CF-1酶原不能自催化激活。两种组织蛋白酶都能水解人血红蛋白，但它们的联合作用比单独使用一种酶更有效地将血红蛋白降解为更小的肽。在生理ph值下，Ov-CF-1比Ov-CB-1更有效地降解细胞外基质蛋白。我们认为Ov-CB-1调节Ov-CF-1的活性，并且这两种酶共同降解宿主组织，促进肝吸附虫相关胆管癌的发展。
Opisthorchis viverrini is an important helminth pathogen of humans that is endemic in Thailand and Laos. Adult flukes reside within host bile ducts and feed on epithelial tissue and blood cells. Chronic opisthorchiasis is associated with severe hepatobiliary diseases such as cholangiocarcinoma. Here we report that adult O. viverrini secrete two major cysteine proteases: cathepsin F (Ov-CF-1) and cathepsin B1 (Ov-CB-1). Ov-CF-1 is secreted as an inactive zymogen that auto-catalytically processes and activates to a mature enzyme at pH 4.5 via an intermolecular cleavage at the prosegment-mature domain junction. Ov-CB-1 is also secreted as a zymogen but, in contrast to Ov-CF-1, is fully active against peptide and macromolecular substrates despite retaining the N-terminal prosegment. The active Ov-CB-1 zymogen was capable of trans-activating Ov-CF-1 by proteolytic removal of its prosegment at pH 5.5, a pH at which the Ov-CF-1 zymogen cannot auto-catalytically activate. Both cathepsins hydrolyse human haemoglobin but their combined action more efficiently degrades haemoglobin to smaller peptides than each enzyme alone. Ov-CF-1 degraded extracellular matrix proteins more effectively than Ov-CB-1 at physiological pH. We propose that Ov-CB-1 regulates Ov-CF-1 activity and that both enzymes work together to degrade host tissue contributing to the development of liver fluke-associated cholangiocarcinoma.
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DOI：
10.1007/978-1-60327-530-9_15
发表时间：
2009-01-01
期刊：
INFLAMMATION AND CANCER: METHODS AND PROTOCOLS, VOL 2: MOLECULAR ANALYSIS AND PATHWAYS
影响因子：
--
作者：
Mon, Naing Naing;Kokuryo, Toshio;Hamaguchi, Michinari
通讯作者：
Hamaguchi, Michinari
影响因子：
4
作者：
Dvorák, J;Delcroix, M;Caffrey, CR
通讯作者：
Caffrey, CR
影响因子：
2.1
作者：
GABAY, T;GINSBURG, H
通讯作者：
GINSBURG, H
影响因子：
11.2
作者：
Farazi, Paraskevi A.;Zeisberg, Michael;DePinho, Ronald A.
通讯作者：
DePinho, Ronald A.
影响因子：
4.8
作者：
Collins, PR;Stack, CM;Donnelly, S
通讯作者：
Donnelly, S