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MDM2, MDMX and p53 in oncogenesis and cancer therapy.

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TLDR
This Review highlights the progress made and pitfalls encountered as the field continues to search for MDM-targeted antitumour agents.
Abstract
The MDM2 and MDMX (also known as HDMX and MDM4) proteins are deregulated in many human cancers and exert their oncogenic activity predominantly by inhibiting the p53 tumour suppressor. However, the MDM proteins modulate and respond to many other signalling networks in which they are embedded. Recent mechanistic studies and animal models have demonstrated how functional interactions in these networks are crucial for maintaining normal tissue homeostasis, and for determining responses to oncogenic and therapeutic challenges. This Review highlights the progress made and pitfalls encountered as the field continues to search for MDM-targeted antitumour agents.

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Electrochemical Methods for the Analysis of Clinically Relevant Biomolecules

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References
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Journal ArticleDOI

Comprehensive genomic characterization defines human glioblastoma genes and core pathways

Roger E. McLendon, +233 more
- 23 Oct 2008 - 
TL;DR: The interim integrative analysis of DNA copy number, gene expression and DNA methylation aberrations in 206 glioblastomas reveals a link between MGMT promoter methylation and a hypermutator phenotype consequent to mismatch repair deficiency in treated gliobeasts, demonstrating that it can rapidly expand knowledge of the molecular basis of cancer.
Journal ArticleDOI

The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity

TL;DR: The results indicate that large, annotated cell-line collections may help to enable preclinical stratification schemata for anticancer agents and the generation of genetic predictions of drug response in the preclinical setting and their incorporation into cancer clinical trial design could speed the emergence of ‘personalized’ therapeutic regimens.
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In vivo activation of the p53 pathway by small-molecule antagonists of MDM2.

TL;DR: In this article, the authors identify potent and selective small-molecule antagonists of MDM2 and confirm their mode of action through the crystal structures of complexes, leading to cell cycle arrest, apoptosis, and growth inhibition of human tumor xenografts.
Journal ArticleDOI

The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation

TL;DR: A product of the mdm-2 oncogene forms a tight complex with the p53 protein, and the mDM-2oncogene can inhibit p53-mediated transactivation.
Journal ArticleDOI

RING Domain E3 Ubiquitin Ligases

TL;DR: RING E3s have been linked to the control of many cellular processes and to multiple human diseases, and knowledge of the physiological partners, biological functions, substrates, and mechanism of action for most RING E 3s remains at a rudimentary stage.
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Which diseases have MDM2-MDMX dysfunction?

MDM2-MDMX dysfunction is associated with many human cancers due to their oncogenic activity inhibiting p53, highlighting their role in oncogenesis and cancer therapy.