Trp53 regulates Notch 4 signaling through Mdm2.
Notch receptors and their ligands have crucial roles in development and tumorigenesis. We present evidence demonstrating the existence of an antagonistic relationship between Notch 4 and Trp53, which is controlled by the Mdm2-dependent ubiquitylation and degradation of the Notch receptor. We show that this signal-controlling mechanism is mediated by physical ... interactions between Mdm2 and Notch 4 and suggest the existence of a trimeric complex between Trp53, Notch 4 and Mdm2, which ultimately regulates Notch activity. Functional studies indicate that Trp53 can suppress NICD4-induced anchorage-independent growth in mammary epithelial cells and present evidence showing that Trp53 has a pivotal role in the suppression of Notch-associated tumorigenesis in the mammary gland.
Mesh Terms:
Animals, Cell Line, Epithelial Cells, Humans, Mice, Protein Binding, Protein Structure, Tertiary, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-mdm2, Receptors, Notch, Signal Transduction, Tumor Suppressor Protein p53
Animals, Cell Line, Epithelial Cells, Humans, Mice, Protein Binding, Protein Structure, Tertiary, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-mdm2, Receptors, Notch, Signal Transduction, Tumor Suppressor Protein p53
J. Cell. Sci.
Date: Apr. 01, 2011
PubMed ID: 21402876
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- Interactions 2
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