Targeting the interaction between tumor suppressor p53 and murine double minute 2(MDM2) has been an attractive therapeutic strategy of recent cancer research. There are a few number MDM2-targeted anticancer drug molecules undergoing clinical trials, yet none them have approved so far. In this study, new approach is employed in which dynamics MDM2 obtained by elastic network models used as guide...

conclusions our findings indicated that mdm2 40-bp ins/del polymorphism was not associated with all in our iranian population. further studies with larger sample sizes and diverse ethnicities are required to verify our findings. background the human murine double minute 2 (mdm2), an oncoprotein, is the major negative regulator of p53. objectives the purpose of this study was to evaluate the imp...

Rational design for a new spiroxindoles, combined with benzimidazole scaffold to identify murine double minute two (MDM2) inhibitor was synthesized and characterized. The desired spiroxindoles were achieved via [3+2] cycloaddition reaction approach which afforded the cycloadducts four asymmetric centers separated in an excellent regioselective diastereoselective compound. subjected set of bioch...

The protein (MDM2) coded by the mouse double minute-2 (mdm2) gene or its human homologue is well known as an oncoprotein. Malignant human tumors particularly breast tumors and soft tissue sarcomas frequently overexpress MDM2. Artificial amplification of mdm2 gene derived from a transformed murine cell line enhances tumorigenic potential of murine cells. Consistent with its tumorigenic property,...

p14ARF tumour suppressor stabilises and activates p53 by directly interacting with (H)Mdm2 [(human) murine double minute 2 homologue] and inhibiting its E3 ubiquitin ligase activity. Here we demonstrate that p14ARF promotes accumulation of (H)Mdm2 conjugated to the small ubiquitin-like protein SUMO-1. Mutational analysis demonstrated that the N-terminus of Mdm2 is a target for p14ARF-mediated S...

Two RING fingers and DRIL1 (TRIAD1) is a proapoptotic protein that promotes p53 activation in several cancer cell lines, including MCF7, U2OS and A549 cells. In this study, we demonstrated that TRIAD1 is a novel ubiquitination target for proteasome-dependent degradation by murine double minute 2 (MDM2). TRIAD1 was found to interact with and be ubiquitinated by MDM2. RNA interference against MDM...

Murine double minute homolog 2 (MDM2) is an oncoprotein that induces p53 degradation via ubiquitin‑ligase activity. MDM4 cooperates with MDM2‑mediated degradation, directly inhibiting transcription by binding to its transactivation domain. Our previous study reported the simultaneous inhibition of MDM2 and using nutlin‑3 (an inhibitor MDM2‑p53 interaction) chimeric small interfering RNA DNA‑sub...

The murine double minute 2 (mdm2) gene encodes a negative regulator of the p53 tumor suppressor. Amplification of mdm2 or increased expression by unknown mechanisms occurs in many tumors. Thus, increased levels of MDM2 would inactivate the apoptotic and cell cycle arrest functions of p53, as do deletion or mutation of p53, common events in the genesis of many kinds of tumors. MDM2 functions as ...

Murine double minute 2 (Mdm2) is a critical component of the responses to both ionizing and UV radiation. The level of Mdm2 expression determines the extent to which radiation induces an increase in the activity of the p53 tumor suppressor. Mdm2 acts as a survival factor in many cell types by limiting the apoptotic function of p53. In addition, expression of mdm2 is induced in response to DNA d...

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...