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 original | English |
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Páginas (desde-hasta) | 1094-1108 |
Número de páginas | 15 |
Publicación | Oncotarget |
Volumen | 2 |
N.º | 12 |
DOI | |
Estado | Published - dic. 2011 |
ASJC Scopus Subject Areas
- Oncology
PubMed: MeSH publication types
- Journal Article
- Research Support, Non-U.S. Gov't
- Retracted Publication