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.
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. It is believed that further MDM2 research and therapy could possibly lead to an anticancer strategy [1].
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 [2].
