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

• Published in: Cancer investigation 2017-05, Vol.35 (5), p.301-312
• Main Authors: Kendig, Robert D., Kai, Fumitake, Fry, Elizabeth A., Inoue, Kazushi
• Format: Article
• Language: English
• Subjects: A549 Cells; Animals; Apoptosis Regulatory Proteins - genetics; Apoptosis Regulatory Proteins - metabolism; Bbc3; Binding Sites; Cancer; Cell Nucleus - drug effects; Cell Nucleus - metabolism; Chromatin immunoprecipitation; Cip1; Cyclin-Dependent Kinase Inhibitor p21 - genetics; Cyclin-Dependent Kinase Inhibitor p21 - metabolism; Dmp1 (Dmtf1); DNA - metabolism; DNA binding; DNA Damage; Doxorubicin - pharmacology; Electrophoretic mobility shift assay (EMSA); Genotype; Humans; Knockout; Mdm2; Mice; Mice, Knockout; NIH 3T3 Cells; Phenotype; Promoter Regions, Genetic; Protein Binding; Thbs1; Thrombospondin 1 - genetics; Thrombospondin 1 - metabolism; Time Factors; Transcription; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription, Genetic; Tumor Suppressor Protein p53 - deficiency; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism
• ISSN: 0735-7907; 1532-4192; 1532-4192
• DOI: 10.1080/07357907.2017.1303505

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.