A nucleoside diphosphate kinase A (nm23-H1) serine 120-->glycine substitution in advanced stage neuroblastoma affects enzyme stability and alters protein-protein interaction

Oncogene. 1996 Feb 1;12(3):659-67.


A high level of nucleoside diphosphate kinase A (NDPK A/nm23-H1) in neuroblastoma is associated with advanced stage disease. We have also found a serine 120-->glycine substitution in NDPK A and/or amplification of the nm23-H1 gene in advanced stage neuroblastomas. Serine 120, a highly conserved residue, is located in proximity to histidine 118 which forms a phosphorylated intermediate essential for NDPK activity. The effect of Ser120-->Gly substitution on the biochemical properties of NDPK A was investigated. Phosphate-transferase activity was lower in the recombinant mutant NDPK A and in the immunoprecipitated complex consisting of NDPK A and NDPK B prepared from a neuroblastoma tumor containing the mutation, relative to the wild-type. There was a significant decrease in the enzyme stability toward urea- or temperature-induced denaturation for the recombinant mutant NDPK A and in an immunoprecipitate from a tumor containing the mutation. Recombinant NDPK A containing the Ser120-->Gly mutation exhibited reduced hexameric and increased dimeric oligomerization relative to the wild-type. Moreover a 28 kDa cellular protein was detected, that co-precipitated with the mutant but not wild-type NDPK A. The altered properties of the mutant protein may have relevance to a role for NDPK A in neuroblastoma progression.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Cross-Linking Reagents
  • DNA Primers
  • Enzyme Stability
  • Glutaral
  • Glycine*
  • Hot Temperature
  • Humans
  • Isoenzymes / chemistry
  • Isoenzymes / isolation & purification
  • Isoenzymes / metabolism
  • Kinetics
  • Molecular Sequence Data
  • Monomeric GTP-Binding Proteins*
  • Mutagenesis, Site-Directed
  • NM23 Nucleoside Diphosphate Kinases
  • Neoplasm Staging
  • Neuroblastoma / enzymology*
  • Neuroblastoma / genetics*
  • Neuroblastoma / pathology
  • Nucleoside-Diphosphate Kinase / chemistry
  • Nucleoside-Diphosphate Kinase / metabolism
  • Point Mutation*
  • Polymerase Chain Reaction
  • Protein Denaturation
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / metabolism
  • Serine*
  • Thermodynamics
  • Transcription Factors / chemistry*
  • Transcription Factors / isolation & purification
  • Transcription Factors / metabolism*


  • Cross-Linking Reagents
  • DNA Primers
  • Isoenzymes
  • NM23 Nucleoside Diphosphate Kinases
  • Recombinant Proteins
  • Transcription Factors
  • Serine
  • NME1 protein, human
  • Nucleoside-Diphosphate Kinase
  • Monomeric GTP-Binding Proteins
  • Glutaral
  • Glycine