Background: Breast cancer is one of the most common cancers among women worldwide. Tumor protein 53 (TP53) and its regulator the mouse double murine 2 (MDM2) have important roles in tumorigenesis by playing key roles in cell division and response to DNA damage. MDM2 SNP309 T>G (rs2279744) polymorphism in the promoter region of MDM2 gene can cause dysfunction and inactivation of TP53 which promo...

The mdm2 oncogene encodes p90(MDM2), which binds to and inactivates the p53 tumor suppressor protein. p90(MDM2) inhibits p53 by blocking the transcriptional activation domain of p53 as well as by stimulating its degradation. Recently, we showed that another product of the wild-type mdm2 gene, p76(MDM2), lacks the first 49 amino acids of p90(MDM2) and cannot bind p53. Here, we report that, like ...

Background: Gastric cancer (GC) is considered as one of the most common types of cancer worldwide with poor prognosis and generally limited treatment options. Recent studies have indicated that HER2, MDM2, MYC, MET, and TP53 play an important role in the development of gastric cancer. Therefore, the aim of this study was to evaluate the incidence of amplification/deletion of these genes in pati...

Human cancers over-expressing mdm2, through a T to G variation at a single nucleotide polymorphism at position 309 (mdm2 SNP309), have functionally inactivated p53 that is not effectively degraded. They also have high expression of the alternatively spliced transcript, mdm2-C. Alternatively spliced mdm2 transcripts are expressed in many forms of human cancer and when they are exogenously expres...

Estrogen receptor beta (ERβ) is an isoform of estrogen that plays a role in breast cancer. An E3 ubiquitin ligase, murine double minute 2 (MDM2), can bind to ERβ and degrade it. Virtual screening protein-protein docking studies are one the approaches be performed discover FDA-approved drugs targeting interaction ERβ-MDM2 complex. This study aimed conduct virtual 1615 compounds between as initia...

background : mdm2, e-cadherin, survivin and her2 genes are involved in the regulation of normal cell growth. however, any crucial change in their expression levels can convert a normal cell into a cancer cell. numerous studies have identified alterations of these gene expression levels in various cancers, particularly in breast cancer. thus, they may be used as diagnostic biomarkers. in this ex...

The Mdm2 oncoprotein promotes p53 ubiquitination and destruction. Yet, exact molecular mechanisms of Mdm2 destruction itself, under DNA damaging conditions, remain unclear. Recently, we identified SCFβ-TRCP as a novel E3 ligase that targets Mdm2 for ubiquitination and destruction in a Casein Kinase Iδ (CKIδ)-dependent manner. However, it remains elusive how the β-TRCP/CKIδ/Mdm2 signaling axis i...

<sec>P53 is well recognized to be a tumor suppressor protein. In response the external stress or environmental perturbation, p53 can promote transcription of various target genes downstream, thus regulating cell cycle, apoptosis, DNA repair, and angiogenesis. However, activation further activated by another protein, MDM2, which negatively regulates level inverse reduces p53. This phenomen...

Inhibition of murine double minute 2 (MDM2)-p53 protein-protein interaction with small molecules has been shown to reactivate p53 and inhibit tumor growth. Here, we describe rational, structure-guided, design novel isoindolinone-based MDM2 inhibitors. X-ray crystallography, quantum mechanics ligand-based design, metabolite identification all contributed toward the discovery potent in vitro vivo...

Of the >40 alternative and aberrant splice variants of MDM2 that have been described to date, the majority has lost both the well-characterized nuclear localization signal (NLS1) and the nuclear export signal (NES) sequence. Because cellular localization of proteins provides insight regarding their potential function, we determined the localization of three different MDM2 splice variants. The s...