【摘 要】
：
The molecule Atg4 is a cysteine protease of the C54 family and plays essential roles in the autophagy process.Therefore,Atg4 activity is important for autophagy and could be an attractive target for t
【机 构】
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School of Pharmaceutical Sciences,Sun Yat-Sen University,Guangzhou,510006
【出 处】
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中国生物化学与分子生物学会2016年全国学术会议
论文部分内容阅读
The molecule Atg4 is a cysteine protease of the C54 family and plays essential roles in the autophagy process.Therefore,Atg4 activity is important for autophagy and could be an attractive target for therapeutic intervention.Thus,the identification of specific Atg4 inhibitors has proven highly challenging.In this study,we for the first time screened Atg4 inhibitors both targeting at Atg4B and Atg4A.By performing in silico docking based on the structure of Atg4B and verified by FRET and SDS-PAGE assay in vitro,we identified six small molecule compounds that both inhibit Atg4B and Atg4A activity while having no effect on caspase-3.SYSU-00130 and XOS00201 effectively inhibited Atg4 activity in vitro and had anti-proliferative efficacy in various cancer cells.Moreover,SYSU-00130 and XOS00201 induced autophagy in a time dependent manner.Overall,in silico analysis and in vitro experimental validation together demonstrate that SYSU-00130 and XOS00201 can target Atg4 and have a negative effect on cancer cell viability which might be caused by the impaired autophagy.These results suggest that ATG4 might be a potential drug target for cancer therapy.
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