Stabilization of the p53-DNA Complex by the Nuclear Protein Dmp1α

We recently reported the existence of a physical interaction between the Myb-like transcription factor Dmp1 (Dmtf1) and p53 in which Dmp1 antagonized polyubiquitination of p53 by Mdm2 and promoted its nuclear localization. Dmp1 significantly stabilized p53-DNA complexes on promoters that contained p53-consensus sequences, which were either supershifted or disrupted with antibodies to Dmp1. Lysates from mice injected with doxorubicin showed that Dmp1 bound to p21^Cip1, Bbc3, and Thbs1 gene regulatory regions in a p53-dependent fashion. Our data suggest that acceleration of DNA-binding of p53 by Dmp1 is a critical process for Dmp1 to increase the p53 function in Arf-deficient cells.