Menin, a gene product responsible for multiple endocrine neoplasia type 1, interacts with the putative tumor metastasis suppressor nm23

Biochem Biophys Res Commun. 2001 Apr 20;282(5):1206-10. doi: 10.1006/bbrc.2001.4723.


Although the gene responsible for multiple endocrine neoplasia type 1 (MEN1) has been identified, the function of its gene product, menin, is unknown. To examine the biological role of the MEN1 gene, we searched for associated proteins with a yeast two-hybrid system using the MEN1 cDNA fragment as bait. On screening a rat fetal brain embryonic day 17 library, in which a high level of MEN1 expression was detected, we identified a putative tumor metastasis suppressor nm23/nucleoside diphosphate (NDP) kinase as an associated protein. This finding was confirmed by in vitro interaction assays based on glutathione S-transferase pull down experiments. The association required almost the entire menin protein, and several missense MEN1 mutations reported in MEN1 patients caused a loss of the binding activity for nm23. This result suggests that this interaction may play important roles in the biological functions of the menin protein, including tumor suppressor activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COS Cells
  • Cell-Free System
  • Genes, Tumor Suppressor / genetics
  • Glutathione Transferase / genetics
  • Methionine / metabolism
  • Monomeric GTP-Binding Proteins / metabolism*
  • Multiple Endocrine Neoplasia Type 1 / etiology*
  • Multiple Endocrine Neoplasia Type 1 / genetics
  • Mutation, Missense / genetics
  • NM23 Nucleoside Diphosphate Kinases
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Nucleoside-Diphosphate Kinase*
  • Protein Binding / physiology
  • Protein Structure, Tertiary / physiology
  • Proto-Oncogene Proteins*
  • Rats
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Sulfur Radioisotopes
  • Transcription Factors / metabolism*
  • Two-Hybrid System Techniques


  • MEN1 protein, human
  • NM23 Nucleoside Diphosphate Kinases
  • Neoplasm Proteins
  • Proto-Oncogene Proteins
  • Recombinant Fusion Proteins
  • Sulfur Radioisotopes
  • Transcription Factors
  • Methionine
  • Glutathione Transferase
  • NME1 protein, human
  • Nucleoside-Diphosphate Kinase
  • Monomeric GTP-Binding Proteins