Murine double minute 2: p53-independent roads lead to genome instability or death

Abstract

The oncoprotein murine double minute 2 (Mdm2) is frequently overexpressed in many types of human malignancies. Although Mdm2 has an essential role in negatively regulating the p53 tumor suppressor, it also has less well characterized p53-independent functions that influence pathways that are crucial for controlling tumorigenesis. In addition to the impact Mdm2 has on p53-independent apoptosis, mounting evidence is linking increased Mdm2 levels to altered cell-cycle regulation, DNA replication and DNA repair leading to loss of genome stability. Mdm2 involvement in pathways that influence chromosome stability and cell death, distinct from its role in the p53 pathway, strengthens the position of Mdm2 as a desirable therapeutic target for the treatment of human cancers.