XPB, a subunit of TFIIH, is a target of the natural product triptolide.
Nat Chem Biol
; 7(3): 182-8, 2011 Mar.
Article
en En
| MEDLINE
| ID: mdl-21278739
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fenantrenos
/
Productos Biológicos
/
ADN Helicasas
/
Diterpenos
/
Proteínas de Unión al ADN
/
Factor de Transcripción TFIIH
/
Antineoplásicos
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Nat Chem Biol
Asunto de la revista:
BIOLOGIA
/
QUIMICA
Año:
2011
Tipo del documento:
Article
País de afiliación:
Estados Unidos