Activated Notch1 interacts with p53 to inhibit its phosphorylation and transactivation

Cited 0 time in webofscience Cited 0 time in scopus
  • Hit : 433
  • Download : 300
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.
Publisher
Nature Publishing Group
Issue Date
2007-05-14
Keywords

p53; Notch; apoptosis; phosphorylation

Citation

Cell Death Differentiation, Vol.14, pp.982-991

DOI
10.1038/sj.cdd.4402083
URI
http://hdl.handle.net/10203/10709
Appears in Collection
BS-Conference Papers(학술회의논문)

qr_code

  • mendeley

    citeulike


rss_1.0 rss_2.0 atom_1.0