Cytocidal actions of parasporin-2, an anti-tumor crystal toxin from Bacillus thuringiensis
Cytocidal actions of parasporin-2, an anti-tumor crystal toxin from Bacillus thuringiensis
复制标题
DOI：
10.1074/jbc.m602589200
复制
发表时间：
2006-09-08
影响因子：
4.8
通讯作者：
Ito, Akio
中科院分区：
文献类型：
--
作者：
Kitada, Sakae;Abe, Yuichi;Ito, Akio
副孢子蛋白-2是一种新的晶体蛋白，来源于非杀虫性和非溶血性的苏云金芽孢杆菌，识别并杀死人类肝癌和结肠癌细胞以及某些类别的人类培养细胞。在这里，我们报告说，一个有效的蛋白酶K-耐parasporin-2毒素显示出特异性结合和多种细胞杀伤作用对人类肝细胞癌细胞。裂解的N-末端区域的parasporin-2是必不可少的毒素活性，而C-末端消化所需的快速细胞损伤。蛋白酶激活的parasporin-2诱导显着的形态学改变，细胞起泡，细胞骨架的变化，线粒体和内质网碎片。毒素处理后，质膜透性立即增加，大部分细胞质蛋白从细胞中泄漏，而线粒体和内质网蛋白仍留在中毒细胞。在肝肿瘤组织切片和易感的人类培养细胞中，副孔蛋白-2选择性地与癌细胞结合，并定位在质膜上，直到细胞受损。因此，副孔蛋白-2作为细胞溶解素，其以靶细胞特异性使质膜透化，随后诱导细胞衰变。
Parasporin-2, a new crystal protein derived from noninsecticidal and nonhemolytic Bacillus thuringiensis, recognizes and kills human liver and colon cancer cells as well as some classes of human cultured cells. Here we report that a potent proteinase K-resistant parasporin-2 toxin shows specific binding to and a variety of cytocidal effects against human hepatocyte cancer cells. Cleavage of the N-terminal region of parasporin-2 was essential for the toxin activity, whereas C-terminal digestion was required for rapid cell injury. Protease-activated parasporin-2 induced remarkable morphological alterations, cell blebbing, cytoskeletal alterations, and mitochondrial and endoplasmic reticulum fragmentation. The plasma membrane permeability was increased immediately after the toxin treatment and most of the cytoplasmic proteins leaked from the cells, whereas mitochondrial and endoplasmic reticulum proteins remained in the intoxicated cells. Parasporin-2 selectively bound to cancer cells in slices of liver tumor tissues and susceptible human cultured cells and became localized in the plasma membrane until the cells were damaged. Thus, parasporin-2 acts as a cytolysin that permeabilizes the plasma membrane with target cell specificity and subsequently induces cell decay.