雷公藤甲素
转录因子ⅡH
蛋白质亚单位
作用机理
天然产物
生物
分子生物学
化学
抄写(语言学)
细胞生物学
核苷酸切除修复
生物化学
DNA
DNA损伤
基因
细胞凋亡
语言学
哲学
体外
作者
Denis V. Titov,Benjamin Gilman,Qing‐Li He,Shridhar Bhat,Woon Kai Low,Yongjun Dang,Michael B. Smeaton,Arnold L. Demain,Paul S. Miller,Jennifer F. Kugel,James A. Goodrich,Jun O. Liu
摘要
Triptolide (1) is a structurally unique diterpene triepoxide isolated from a traditional Chinese medicinal plant with anti-inflammatory, immunosuppressive, contraceptive and antitumor activities. Its molecular mechanism of action, however, has remained largely elusive to date. We report that triptolide covalently binds to human XPB (also known as ERCC3), a subunit of the transcription factor TFIIH, and inhibits its DNA-dependent ATPase activity, which leads to the inhibition of RNA polymerase II-mediated transcription and likely nucleotide excision repair. The identification of XPB as the target of triptolide accounts for the majority of the known biological activities of triptolide. These findings also suggest that triptolide can serve as a new molecular probe for studying transcription and, potentially, as a new type of anticancer agent through inhibition of the ATPase activity of XPB.
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