Journal of Bioenergetics and Biomembranes

, Volume 32, Issue 3, pp 277–284

Human NM23/Nucleoside Diphosphate Kinase Regulates Gene Expression through DNA Binding to Nuclease-Hypersensitive Transcriptional Elements

  • Edith H. Postel
  • Steven J. Berberich
  • John W. Rooney
  • David M. Kaetzel


NM23-H2/NDP kinase B has been identified as a sequence-specific DNA-binding protein withaffinity for a nuclease-hypersensitive element of the c-MYC gene promoter (Postel et al.,1993). The ability of Nm23-H2 to activate c-MYC transcription in vitro and in vivo via thesame element demonstrates the biological significance of this interaction. Mutational analyseshave identified Arg34, Asn69 and Lys135 as critical for DNA binding, but not required forthe NDP kinase reaction. However, the catalytically important His118 residue is dispensiblefor sequence-specific DNA binding, suggesting that sequence-specific DNA recognition andphosphoryl transfer are independent properties. Nm23-H2 also has an activity that cleavesDNA site-specifically, involving a covalent protein-DNA complex. In a DNAsequence-dependent manner, Nm23-H2 recognizes additional target genes for activation, includingmyeloperoxidase, CD11b, and CCR5, all involved in myeloid-specific differentiation. Moreover,both NM23-H1 and Nm23-H2 bind to nuclease hypersensitive elements in the platelet-derivedgrowth factor PDGF-A gene promoter sequence-specifically, correlating with either positiveor negative transcriptional regulation. These data support a model in which NM23/NDP kinasemodulates gene expression through DNA binding and subsequent structural transactions.

NM23 PuF transcription c-MYC nuclease-hypersensitive PDGF differentiation 


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Copyright information

© Plenum Publishing Corporation 2000

Authors and Affiliations

  • Edith H. Postel
    • 1
  • Steven J. Berberich
    • 2
  • John W. Rooney
    • 3
  • David M. Kaetzel
    • 4
  1. 1.Department of Molecular BiologyPrinceton UniversityPrinceton
  2. 2.Department of Biochemistry and Molecular BiologyWright State UniversityDayton
  3. 3.Department of MicrobiologyColumbia University College of Physicians & SurgeonsNew York
  4. 4.Department of Pharmacology, College of Medicine, Chandler Medical CenterUniversity of KentuckyLexington

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