background: fragile histidine triad protein (fhit), as a known tumor suppressor protein, has been proposed to play crucial role in inhibiting p53 degradation by mdm2. studies have confirmed fhit interaction with p53 or mdm2, although functional interacting domains of fhit with mdm2 and/or p53 are not completely defined. thus, through determining the significant structural interacting domains of...

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...

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...

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...

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...

The MDM2 protein regulates the functional activity of the p53 tumor suppressor through direct physical association. Signals that control MDM2 expression are poorly understood but are likely to play an important role in the regulation of p53 activity. We show here that the half-life of MDM2 protein is shorter in proliferating than in quiescent peripheral blood mononuclear cells. We also demonstr...

<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...

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...

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...