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Function

MDM2 is an E3 ubiquitin ligase that is specific to the p53 pathway. MDM2 is one of the main negatively regulatory proteins of the p53 pathway. The interaction between MDM4 and p53 can be seen in Data involving MDM2 and the SNP285 polymorphism within its promotor region have been researched and is significantly linked to a decreased cancer risk^[1].

Relevance

Often, the p53 pathway is compromised due to the inactivation of MDM2 which is thought to be one of the lead causes of tumor progression. Data involving MDM2 and the SNP285 polymorphism within its promotor region have been researched, and this region has been shown to be significantly linked to a decreased cancer risk^[2]. It is believed that further MDM2 research and therapy could possibly lead to an anticancer strategy ^[3].

Structural highlights

Although there is a lot of research currently underway that involves the MDM2-p53 interactions, it is unsure exactly how these two molecules interact. This is because part of MDM2’s receptor structure contains highly flexible parts. There is evidence that has shown that as the binding with p53 occurs, the MDM2 structure changes conformation from “closed” to “open.” In the closed conformation, there is an N-terminus fragment (residues 25-109) that forms a lid that covers its hydrophobic binding site. This shows that there are many intermediate levels of binding for the MDM2 complex. During the interaction with p53, it is thought that the N-terminus fragment interacts with a short, helical region of p53 ^[4].