Typical three-domain cry proteins of Bacillus thuringiensis strain A1462 exhibit cytocidal activity on limited human cancer cells
Typical three-domain cry proteins of Bacillus thuringiensis strain A1462 exhibit cytocidal activity on limited human cancer cells
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DOI：
10.1093/jb/mvi177
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发表时间：
2005-12-01
影响因子：
2.7
通讯作者：
Ito, A
中科院分区：
文献类型：
--
作者：
Yamashita, S;Katayama, H;Ito, A
苏云金芽孢杆菌A1462菌株产生两个分子质量为88 kDa的副孢包涵蛋白，经蛋白酶K消化激活后转化为64 kDa的毒素。两种毒素对两种人类癌细胞系HL60（髓性白血病细胞）和HepG2（肝癌细胞）均表现出较强的杀伤活性，而对11种人类和3种哺乳动物细胞系（包括4种非癌细胞系）均表现出低毒性或无毒性。两种毒素对敏感细胞的细胞毒性表现为细胞迅速肿胀。基因克隆实验获得了两个编码88-kDa Cry蛋白的新基因Cry41Aa和Cry41Ab。这两个蛋白的氨基酸序列包含5个在苏云金芽孢杆菌杀虫Cry蛋白中普遍保守的片段区。这是首次报道典型的三结构域Cry蛋白具有优先于癌细胞的细胞杀细胞活性。
Bacillus thuringiensis strain A1462 produced two parasporal inclusion proteins with a molecular mass of 88 kDa that were converted to 64-kDa toxins when activated by proteinase K digestion. Both toxins exhibited strong cytocidal activity against two human cancer cell lines, HL60 (myeloid leukemia cells) and HepG2 (liver cancer cells), while low or no toxicities were observed against 11 human and three mammalian cell lines, including four non-cancer cell lines. The cytotoxicity of both toxins on susceptible cells was characterized by rapid cell swelling. Gene cloning experiments provided two novel genes encoding 88-kDa Cry proteins, Cry41Aa and Cry41Ab. The amino acid sequences of the two proteins contain five block regions commonly conserved in B. thuringiensis insecticidal Cry proteins. This is the first report of the occurrence of typical three-domain Cry proteins with cytocidal activity preferential for cancer cells.