Yamashita Satoko, Katayama Hideki, Saitoh Hiroyuki, Akao Tetsuyuki, Park Yu Shin, Mizuki Eiichi, Ohba Michio, Ito Akio
Biotechnology & Food Research Institute, Fukuoka Industrial Technology Center, Fukuoka.
J Biochem. 2005 Dec;138(6):663-72. doi: 10.1093/jb/mvi177.
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.
苏云金芽孢杆菌菌株A1462产生了两种分子量为88 kDa的伴孢晶体蛋白，经蛋白酶K消化激活后可转化为64 kDa的毒素。这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）均表现出强大的杀细胞活性，而对包括四种非癌细胞系在内的11种人类细胞系和三种哺乳动物细胞系则观察到低毒性或无毒性。两种毒素对敏感细胞的细胞毒性表现为细胞迅速肿胀。基因克隆实验提供了两个编码88 kDa Cry蛋白的新基因，Cry41Aa和Cry41Ab。这两种蛋白质的氨基酸序列包含苏云金芽孢杆菌杀虫Cry蛋白中通常保守的五个区域。这是关于具有优先针对癌细胞的杀细胞活性的典型三结构域Cry蛋白出现的首次报道。
