The Mdm2 oncoprotein is a well-known inhibitor of the p53 tumor suppressor, but it may also possess p53-independent activities. In search of such p53-independent activities, the yeast two-hybrid screen was employed to identify Mdm2-binding proteins. We report that in vitro and in transfected cells, Mdm2 can associate with Numb, a protein involved in the determination of cell fate. This associat...

We here show a new relationship between the human p14ARF oncosuppressor and the MDM2 oncoprotein. MDM2 overexpression in various cancer cell lines causes p14ARF reduction inducing its degradation through the proteasome. The effect does not require the ubiquitin ligase activity of MDM2 and preferentially occurs in the cytoplasm. Interestingly, treatment with inhibitors of the PKC (Protein Kinase...

The human homologue of the mouse double minute 2 (MDM2) oncogene is overexpressed in more than forty different types of malignancies, including solid tumors, sarcomas and leukemias. Because of its prevalent expression and its interactions with p53 and other signaling molecules, MDM2 plays a central role in cancer development and progression. The expression of this oncoprotein is being studied b...

The human murine double minute 2 (MDM2) is known as an oncoprotein through inhibiting P53 transcriptional activity and mediating P53 ubiquitination. Therefore, the amplification of MDM2 may attenuate the P53 pathway and promote tumorigenesis. The SNP309 T>G polymorphism (rs2279744), which is located in the intronic promoter of MDM2 gene, was reported to contribute to the increased level of MDM2...

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...

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...

The Mdm2 oncoprotein physically associates with p53 and antagonizes its tumor suppressor functions. Previous studies indicate that some tumors express alternatively or aberrantly spliced Mdm2 variants that are unable to bind p53, but whether these actively contribute to carcinogenesis or are a byproduct of cancer progression has been unclear. In this study, we examined the ability of full-lengt...

p53 and ARF-INK4a are the two most frequently altered loci in human tumors. The activity of p53 protein is inhibited during normal cell growth by the proto-oncoprotein MDM2 through either repression of p53-mediated transcription in the nucleus or proteasomal degradation of p53 protein in the cytoplasm. Responding to oncogenic signal-activated cell hyperproliferation, ARF-mediated antagonism of ...

The oncoprotein MDM2 negatively regulates the activity and stability of the p53 tumor suppressor and is an important molecular target for anticancer therapy. Aided by mirror image phage display and native chemical ligation, we have previously discovered several proteolysis-resistant duodecimal d-peptide antagonists of MDM2, termed (D)PMI-α, β, γ. The prototypic d-peptide inhibitor (D)PMI-α bind...

p53 is a powerful tumor suppressor and is an attractive cancer therapeutic target because it can be functionally activated to eradicate tumors. The gene encoding p53 protein is mutated or deleted in half of human cancers, which inactivates its tumor suppressor activity. In the remaining cancers with wild-type p53 status, its function is effectively inhibited through direct interaction with the ...