Activated Notch1 interacts with p53 to inhibit its phosphorylation and transactivation
Open Access
- 22 December 2006
- journal article
- research article
- Published by Springer Nature in Cell Death & Differentiation
- Vol. 14 (5) , 982-991
- https://doi.org/10.1038/sj.cdd.4402083
Abstract
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.Keywords
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