Menin, the multiple endocrine neoplasia type 1 gene product, exhibits GTP-hydrolyzing activity in the presence of the tumor metastasis suppressor nm23.
MEN1, the gene responsible for multiple endocrine neoplasia type 1, is a tumor suppressor gene that encodes a protein called menin, of unknown function with no homology to any known protein. Here we demonstrate that menin interacts with a putative tumor metastasis suppressor nm23H1/nucleoside diphosphate (NDP) kinase A in mammalian cells. Given the roles of nm23 as a multi-functional protein, we searched for the possible function of menin. Menin has no effect on the known activities of nm23; that is, nucleoside diphosphate kinase, protein kinase, or GTPase-activating protein for Ras-related GTPase Rad. However, we found that menin hydrolyzes GTP to GDP efficiently in the presence of nm23, whereas nm23 or menin alone shows little or no detectable GTPase activity. Furthermore, menin contains sequence motifs similar to those found in all known GTPases or GTP-binding proteins and shows low affinity but specific binding to GTP/GDP. These results suggest that menin is an atypical GTPase stimulated by nm23.
Yaguchi
Hiroko
H
Growth Factor Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
Ohkura
Naganari
N
Tsukada
Toshihiko
T
Yamaguchi
Ken
K
D020816:Amino Acid Motifs; D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism; D014408:Biomarkers, Tumor; D002460:Cell Line; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism*; D017930:Genes, Reporter; D016147:Genes, Tumor Suppressor; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism*; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics*; D020125:Mutation, Missense; D054778:NM23 Nucleoside Diphosphate Kinases; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009701:Nucleoside-Diphosphate Kinase / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C105373:MEN1 protein, human; D054778:NM23 Nucleoside Diphosphate Kinases; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D006160:Guanosine Triphosphate; C517938:NME1 protein, human; D009701:Nucleoside-Diphosphate Kinase; D020558:GTP Phosphohydrolases; D020559:Monomeric GTP-Binding Proteins