Murine Double Minute (MDM2) Blocks p53-coactivator Interaction, a New Mechanism for Inhibition of p53-dependent Gene Expression

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The Role of Tumor Protein 53 Mutations in Common Human Cancers and Targeting the Murine Double Minute 2–P53 Interaction for Cancer Therapy

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The MDM2-p53 interaction.

Activation of the p53 protein protects the organism against the propagation of cells that carry damaged DNA with potentially oncogenic mutations. MDM2, a p53-specific E3 ubiquitin ligase, is the principal cellular antagonist of p53, acting to limit the p53 growth-suppressive function in unstressed cells. In unstressed cells, MDM2 constantly monoubiquitinates p53 and thus is the critical step in...

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the role of tumor protein 53 mutations in common human cancers and targeting the murine double minute 2–p53 interaction for cancer therapy

the gene tp53 (also known as protein 53 or tumor protein 53), encoding transcription factor p53, is mutated or deleted in half of human cancers, demonstrating the crucial role of p53 in tumor suppression. there are reports of nearly 250 independent germ line tp53 mutations in over 100 publications. the p53 protein has the structure of a transcription factor and, is made up of several domains. t...

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Bypass of abnormal MDM2 inhibition of p53-dependent growth suppression.

Oncoprotein MDM2 inhibits p53-dependent cell cycle arrest and apoptosis. MDM2-overexpressing human cancer cell lines (n = 3) were found to be resistant to growth inhibition after infection by p53-expressing adenovirus (Ad-p53), as compared to low MDM2-expressing tumors (n = 3), in vitro. The growth of MDM2-overexpressing tumors, however, was inhibited by p21-expressing adenovirus (Ad-p21) infec...

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Bypass of Abnormal MDM2 Inhibition of p53-dependent Growth Suppression1

Oncoprotein MDM2 inhibits p53-dependent cell cycle arrest and apoptosis. MDM2-overexpressing human cancer cell lines (n = 3) were found to be resistant to growth inhibition after infection by p53-expressing adenovirus (AdPS3), as compared to low MDM2-expressing tumors (n 3), in vitro. The growth of MDM2-overexpressing tumors, however, was inhibited by p21-expressing adenovirus (Ad-p21) infectio...

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ژورنال

عنوان ژورنال: Journal of Biological Chemistry

سال: 1999

ISSN: 0021-9258

DOI: 10.1074/jbc.274.20.13760