In response to environmental stress, the p53 phosphoprotein is stabilized and activated to inhibit cell growth. p53 stability and activity are negatively regulated by the murine double minute (Mdm2) oncoprotein in an autoregulatory feedback loop. The inhibitory effect of Mdm2 on p53 has to be tightly regulated for proper p53 activity. Phosphorylation is an important level of p53 regulation. In ...

The human p53-binding protein murine double minute 2 (MDM2) is believed to function as a negative regulator of p53. The MDM2 gene was cloned and sequenced only recently and was found to be amplified in a variety of sarcomas. Although mutations in thep5J gene have been shown to occur in human breast carcinoma (HBC), no information is available on MDM2 gene expression in HBC. In this study we rep...

The human homologue of the murine double minute 2 gene (MDM2), a p53-binding protein which may act as a regulator of p53 protein function, has recently heen cloned. Initial studies of this gene in a variety of human tumors have shown frequent gene amplification in most types of sarcomas, including osteosarcomas. Amplification of the MIÃŒM2 gene may produce a functional inactivation of the p53 p...

The human homologue of the murine double minute 2 gene (MDM2), a p53-binding protein which may act as a regulator of p53 protein function, has recently heen cloned. Initial studies of this gene in a variety of human tumors have shown frequent gene amplification in most types of sarcomas, including osteosarcomas. Amplification of the MIÃŒM2 gene may produce a functional inactivation of the p53 p...

The murine double minute-2 (Mdm2) oncoprotein is an E3 ligase and a key regulator of a variety of fundamental cellular processes [1]. Mdm2 was originally identified as being amplified on double-minute chromosomes in transformed mouse fibroblasts [2]. Soon after its discovery, Mdm2 was found to be a negative regulator of tumor suppressor p53. The importance of Mdm2 in controlling the p53 activit...

The expression of the murine double minute-2 (MDM2) gene, the product of which binds to and inactivates p53, was studied in 60 patients with B-cell chronic lymphocytic leukemia (B-CLL) or non-Hodgkin's lymphoma (B-NHL). Northern blot analysis showed that the level of MDM2 gene expression was low in normal human B-cells, whereas 17 of the patients (28.3%) with B-CLL or NHL had more than 10-fold ...

We examined the relationship between p53 mutation, murine double minute 2 (MDM2) gene amplification, and human papillomavirus (HPV) infection in 72 esophageal squamous cell carcinomas. We identified p53 mutations in 29 tumors (40.3%) by PCR-single-strand conformation polymorphism analysis and direct sequencing. Amplification of the MDM2 gene was detected by Southern blot hybridization in 13 (18...

The human E3 ubiquitin ligase murine double minute 2 (MDM2) targets the tumor suppressor p53 for ubiquitination and degradation but also promotes its own ubiquitination and subsequent degradation. As the balance between MDM2 and p53 levels plays a crucial role in regulating cell proliferation and apoptosis, we sought to identify factors selectively inhibiting MDM2 self-ubiquitination. Here we h...

Although TP53 mutations are rare in acute myeloid leukemia (AML), inactivation of wild-type p53 protein frequently occurs through overexpression of its negative regulator MDM2 (murine double minute 2). Recently, small-molecule antagonists of MDM2, Nutlins, have been developed that inhibit the p53-MDM2 interaction and activate p53 signaling. Here, we study the effects of p53 activation by Nutlin...

MDM2 and MDM4, the murine double minute proteins, are oncogenes that function as important regulators of various proteins. One fundamental role for these proteins is regulation of the tumor suppressor, p53. Precise regulation of p53 is vital for coordinated malignant suppression and cell survival. Alternative splice forms of MDM2 as well as MDM4 have been associated with various cancers. Indeed...