Activated Notch1 interacts with p53 to inhibit its phosphorylation and transactivation

Cell Death Differ. 2007 May;14(5):982-91. doi: 10.1038/sj.cdd.4402083. Epub 2006 Dec 22.


We propose a biochemical mechanism for the negative role of Notch signaling on p53 transactivation function. Expression of the intracellular domain of human Notch1 (Notch1-IC) inhibits the expression of p53-responsive genes p21, mdm2, and bax in HCT116 p53(-/-) cells. Furthermore, Notch1-IC expression inhibits the phosphorylation of ectopically expressed p53 in HCT116 p53(-/-) cells as well as the phosphorylation of endogenous p53 in UV-treated HCT116 p53(+/+) cells. Transcriptional downregulation of p53-responsive genes by Notch1-IC was confirmed both by chromatin immunoprecipitation assay and Northern blot analysis. We found the intracellular interaction between Notch1-IC and p53 in HCT116 p53(+/+) cells and suggest that activated Notch1 interaction with p53 is an important cellular event for the inhibition of p53-dependent transactivation. The N-terminal fragment of Notch1-IC, which can interacts with p53, inhibits p53 phosphorylation and represses p53 transactivation. In addition, Notch signaling downregulated p53-dependent apoptosis induced by UV irradiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / radiation effects
  • DNA / metabolism
  • Down-Regulation / radiation effects
  • HCT116 Cells
  • Humans
  • Phosphorylation / radiation effects
  • Protein Binding / radiation effects
  • Receptor, Notch1 / genetics
  • Receptor, Notch1 / metabolism*
  • Repressor Proteins / metabolism
  • Signal Transduction / radiation effects
  • Transcription, Genetic / radiation effects
  • Transcriptional Activation / genetics*
  • Transcriptional Activation / radiation effects
  • Tumor Suppressor Protein p53 / biosynthesis
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Protein p53 / metabolism*
  • Ultraviolet Rays


  • NOTCH1 protein, human
  • Receptor, Notch1
  • Repressor Proteins
  • Tumor Suppressor Protein p53
  • DNA