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Nat Chem Biol. 2011 Mar;7(3):182-8. doi: 10.1038/nchembio.522. Epub 2011 Jan 30.

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

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1
Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

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.

PMID:
21278739
PMCID:
PMC3622543
DOI:
10.1038/nchembio.522
[Indexed for MEDLINE]
Free PMC Article

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