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

Cancer Invest. 2017 May 28;35(5):301-312. doi: 10.1080/07357907.2017.1303505. Epub 2017 Apr 13.

Abstract

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 p21Cip1, 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.

Keywords: Bbc3; Cancer; Chromatin immunoprecipitation; DNA binding; Dmp1 (Dmtf1); Electrophoretic mobility shift assay (EMSA); Knockout; Mdm2; Thbs1; Transcription; p21Cip1; p53.

MeSH terms

  • A549 Cells
  • Animals
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism
  • Binding Sites
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism*
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • DNA / metabolism*
  • DNA Damage
  • Doxorubicin / pharmacology
  • Genotype
  • Humans
  • Mice
  • Mice, Knockout
  • NIH 3T3 Cells
  • Phenotype
  • Promoter Regions, Genetic
  • Protein Binding
  • Thrombospondin 1 / genetics
  • Thrombospondin 1 / metabolism
  • Time Factors
  • 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

Substances

  • Apoptosis Regulatory Proteins
  • Cdkn1a protein, mouse
  • Cyclin-Dependent Kinase Inhibitor p21
  • DMTF1 protein, human
  • Dmtf1 protein, mouse
  • PUMA protein, mouse
  • TP53 protein, human
  • Thrombospondin 1
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • Thbs1 protein, mouse
  • Doxorubicin
  • DNA