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Updated: Jul 18, 2026
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Stimulation of Notch Signaling in Mouse Osteoclast Precursors
Published on: February 28, 2017
Activated Notch1 interacts with p53 to inhibit its phosphorylation and transactivation
1Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, South Korea.
Cell Death and Differentiation
|December 23, 2006
Summary
Notch signaling negatively impacts the tumor suppressor p53. Notch1 intracellular domain (Notch1-IC) inhibits p53 target gene expression and phosphorylation, thereby blocking p53-dependent apoptosis.
Area of Science:
- Molecular Biology
- Cell Signaling
- Cancer Biology
Background:
- The tumor suppressor p53 is a critical regulator of cell cycle arrest, apoptosis, and DNA repair.
- Notch signaling is involved in cell fate determination and has been implicated in various cancers.
- The interplay between Notch signaling and p53 function is not fully understood.
Purpose of the Study:
- To elucidate the biochemical mechanism by which Notch signaling inhibits p53 transactivation function.
- To investigate the effect of Notch1 intracellular domain (Notch1-IC) on p53 phosphorylation and target gene expression.
- To determine the role of Notch signaling in p53-dependent apoptosis.
Main Methods:
- Expression of Notch1-IC in HCT116 p53(-/-) and HCT116 p53(+/+) cells.
- Analysis of p53-responsive gene expression (p21, mdm2, bax) using Northern blot and chromatin immunoprecipitation assays.
- Assessment of p53 phosphorylation in response to Notch1-IC expression and UV irradiation.
- Investigation of intracellular interactions between Notch1-IC and p53.
Main Results:
- Notch1-IC expression inhibited the transcription of p53 target genes p21, mdm2, and bax.
- Notch1-IC suppressed both ectopic and endogenous p53 phosphorylation.
- Direct intracellular interaction between Notch1-IC and p53 was observed, with the N-terminal fragment of Notch1-IC mediating this interaction and inhibiting p53 phosphorylation.
- Notch signaling attenuated UV-induced p53-dependent apoptosis.
Conclusions:
- Activated Notch1 interacts with p53, leading to the inhibition of p53 transactivation and phosphorylation.
- Notch signaling plays a negative regulatory role in p53-dependent apoptosis.
- This study proposes a biochemical mechanism for Notch signaling's suppression of p53 tumor suppressor activity.
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The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
03:14Notch Signaling Pathway
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
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