XPB, a subunit of TFIIH, is a target of the natural product triptolide

Denis V. Titov, Benjamin Gilman, Qing Li He, Shridhar Bhat, Woon Kai Low, Yongjun Dang, Michael Smeaton, Arnold L. Demain, Paul S. Miller, Jennifer F. Kugel, James A. Goodrich, Jun O. Liu

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)182-188
Number of pages7
JournalNature chemical biology
Volume7
Issue number3
DOIs
StatePublished - Mar 2011

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Titov, D. V., Gilman, B., He, Q. L., Bhat, S., Low, W. K., Dang, Y., Smeaton, M., Demain, A. L., Miller, P. S., Kugel, J. F., Goodrich, J. A., & Liu, J. O. (2011). XPB, a subunit of TFIIH, is a target of the natural product triptolide. Nature chemical biology, 7(3), 182-188. https://doi.org/10.1038/nchembio.522