DNA-PKCS binding to p53 on the p21WAF1/CIP1 promoter blocks transcription resulting in cell death

Richard Hill, Patricia A. Madureira, David M. Waisman, Patrick W.K. Lee

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

38 Citas (Scopus)

Resumen

A key determinant of p53-mediated cell fate following various DNA damage modalities is p21WAF1/CIP1 expression, with elevated p21 expression triggering cell cycle arrest and repressed p21 expression promoting apoptosis. We show that under pro-death DNA damage conditions, the DNA-dependent protein kinase (DNA-PKCS) is recruited to the p21 promoter where it forms a protein complex with p53. The DNA-PKCS-associated p53 displays post-translational modifications that are distinct from those under pro-arrest conditions, ablating p21 transcription and inducing cell death. Inhibition of DNA-PK activity prevents DNA-PKCS binding to p53 on the p21 promoter, restores p21 transcription and significantly reduces cell death. These data demonstrate that DNA-PKCS negatively regulates p21 expression by directly interacting with the p21 transcription machinery via p53, driving the cell towards apoptosis.

Idioma originalEnglish
Páginas (desde-hasta)1094-1108
Número de páginas15
PublicaciónOncotarget
Volumen2
N.º12
DOI
EstadoPublished - dic. 2011

ASJC Scopus Subject Areas

  • Oncology

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Retracted Publication

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