The roles of MDM2 and p53

The tumor suppressor protein, p53, often known as the ‘Guardian of the Genome’, regulates cell growth and division and plays a central role in tumor suppression.^1,2 Loss of p53 function – i.e. inhibiting its tumor-suppressor activity – can occur via mutations in the TP53 gene or via downregulation of wild-type p53 through interaction with its primary negative regulator, MDM2.^1,2

The MDM2 oncoprotein, encoded by the mouse double minute 2 (MDM2) gene, plays a key role in maintaining the stability of the p53 signaling pathway by acting as a critical negative regulator of p53.¹ MDM2 promotes p53 degradation and aids tumor proliferation.^1,3 Blocking the MDM2-p53 interaction to restore wild-type p53 function is therefore a potential therapeutic strategy in cancers with wild-type or functional p53.⁴