The regulation of MDM2 oncogene and its impact on human cancers

Yuhan Zhao, Haiyang Yu and Wenwei Hu

Acta Biochim Biophys Sin 2014, March; 46(3): 180–189; doi: 10.1093/abbs/gmt147

Rutgers Cancer Institute of New Jersey, Rutgers the State University of New Jersey, New Brunswick, NJ 08903, USA

Tumor suppressor p53 plays a central role in preventing tumor formation. The levels and activity of p53 is under tight regulation to ensure its proper function. Murine double minute 2 (MDM2), a p53 target gene, is an E3 ubiquitin ligase. MDM2 is a key negative regulator of p53 protein, and forms an auto-regulatory feedback loop with p53. MDM2 is an oncogene with both p53-dependent and p53-independent oncogenic activities, and often has increased expression levels in a variety of human cancers. MDM2 is highly regulated; the levels and function of MDM2 are regulated at the transcriptional, translational and post-translational levels. This review provides an overview of the regulation of MDM2. Dysregulation of MDM2 impacts significantly upon the p53 functions, and in turn the tumorigenesis. Considering the key role that MDM2 plays in human cancers, a better understanding of the regulation of MDM2 will help us to develop novel and more effective cancer therapeutic strategies to target MDM2 and activate p53 in cells.

图例: MDM2表达及活性的调节机制

全文: http://abbs.oxfordjournals.org/content/46/3/180.full 

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