Cleavage of bleomycin hydrolase by caspase-3 during apoptosis

被引:6
作者
Chen, Yang
Xu, Rong
Chen, Jianguo
Li, Xiaoyu
He, Qiyang [1 ,2 ]
机构
[1] Peking Union Med Coll, Inst Med Biotechnol, Beijing 100050, Peoples R China
[2] Chinese Acad Med Sci, Beijing 100050, Peoples R China
关键词
bleomycin hydrolase; apoptosis; caspase-3; protein degradation; CYSTEINE PROTEASE; GENE; RESISTANCE; EXPRESSION; CHEMOTHERAPY; TOXICITY; CLONING;
D O I
10.3892/or.2013.2484
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Bleomycin hydrolase (BLH) affects bleomycin chemotherapy through inactivation of bleomycin with deamination. As a neutral cysteine protease, it also plays various roles in physiological conditions and diseases. However, its mechanism of degradation remains unclear. In the present study, we showed that the levels of BLH were significantly reduced during apoptosis induced by the antitumor agents bleomycin, etoposide and hydroxycamptothecin, and inhibited by the caspase inhibitors Q-VD-oph and Z-DEVD-FMK. Furthermore, the caspase-dependent cleavage of BLH was confirmed by cleavage of partly-purified human BLH with caspase-3 and caspase-9 in vitro. The stability of BLH at normal culture conditions was analyzed with the protein synthesis inhibitor cycloheximide and the proteasome inhibitor MG132. BLH was degraded at a rate lower than that of cyclin D1. This is the first report to demonstrate that BLH is cleaved by caspase-3 during apoptosis.
引用
收藏
页码:939 / 944
页数:6
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