Activated Notch1 interacts with p53 to inhibit its phosphorylation and transactivation

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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
Language
English
Article Type
Article
Keywords

DNA-BINDING FUNCTION; TUMOR-SUPPRESSOR; CHROMOSOMAL TRANSLOCATIONS; NEOPLASTIC TRANSFORMATION; LYMPHOBLASTIC NEOPLASMS; GROWTH ARREST; APOPTOSIS; EXPRESSION; PATHWAY; CELLS

Citation

CELL DEATH AND DIFFERENTIATION, v.14, no.5, pp.982 - 991

ISSN
1350-9047
URI
http://hdl.handle.net/10203/13135
Appears in Collection
BS-Journal Papers(저널논문)
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