Menin, a gene product responsible for multiple endocrine neoplasia type 1, interacts with the putative tumor metastasis suppressor nm23.
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.
Ohkura
N
N
Growth Factor Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. nohkura@gan2.ncc.go.jp
Kishi
M
M
Tsukada
T
T
Yamaguchi
K
K
D000818:Animals; D019556:COS Cells; D002474:Cell-Free System; D016147:Genes, Tumor Suppressor / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics; D008715:Methionine / Q000378:metabolism; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism*; D018761:Multiple Endocrine Neoplasia Type 1 / Q000209:etiology* / Q000235:genetics; D020125:Mutation, Missense / Q000235:genetics; D054778:NM23 Nucleoside Diphosphate Kinases; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009701:Nucleoside-Diphosphate Kinase; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D011518:Proto-Oncogene Proteins; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013462:Sulfur Radioisotopes; D014157:Transcription Factors / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
C105373:MEN1 protein, human; D054778:NM23 Nucleoside Diphosphate Kinases; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D013462:Sulfur Radioisotopes; D014157:Transcription Factors; D008715:Methionine; D005982:Glutathione Transferase; C517938:NME1 protein, human; D009701:Nucleoside-Diphosphate Kinase; D020559:Monomeric GTP-Binding Proteins