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Trp53 regulates Notch 4 signaling through Mdm2.

ABSTRACT: 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.

SUBMITTER: Sun Y

PROVIDER: S-EPMC3056605 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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Trp53 regulates Notch 4 signaling through Mdm2.

Sun Youping Y Klauzinska Malgorzata M Lake Robert J RJ Lee Joseph M JM Santopietro Stefania S Raafat Ahmed A Salomon David D Callahan Robert R Artavanis-Tsakonas Spyros S

Journal of cell science 20110401 Pt 7

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 reg ...[more]

PMID: 21402876

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