Protein 53 (p53) is a important regulator of cell cycle. It most important is the prevention of cancer as it induces "suicide" genes which kill the cell in response to DNA damage. Because of the severe consequences of p53 actions, it must tightly regulated. Murine Double Minute Two (MDM2) and Murine Double Minute Four (MDM2 or MDMx) are responsible for sequestering p53 and preventing its action in mice.
MDM2 and MDMX are highly homologous and both contain p53 binding domain in their N-terminal regions. MDM2 is activated by MDMX through an C-terminal "ring" domain. The p53 binding domain functions the same for both, binding an alpha-helix domain on p53. MDM2 has one more function; it also tags p53 for degradation by proteosomes.
Up-regulation of p53 degradation is present in fifty percent of cancers. Drugs which inhibit the action of MDM2 and/or MDMX would be able to induce apoptosis through the p53 mediated pathway. Currently, the Guida lab is involved in studying compounds which potentially have this function.
A. 
Imidazoloine scaffold of Nutlin inhibitors.
B. 
C. 
B. Nutlin inhibitors (left) and X-ray crystal structure of Nutlin-2 bound to MDM2 (PDB 1111, right).
D. 
Close-up of Nutlin-2 bound to the active site of MDM2.