Nuclear/cytoplasmic localization of the multiple endocrine neoplasia type 1 gene product, menin

Although the gene responsible for multiple endocrine neoplasia, type 1 (MEN 1) has been identified recently, the function of its gene product, menin, i s not known. To examine menin's biological role, we created an N-terminal t agged fusion protein to follow the distribution of menin in the cell. In al l cell lines tested, menin was found both in the nucleus and the cytoplasm, but its localization was dependent on the phase of the cell cycle; during a nondividing phase, menin was found in the nucleus, during and immediately after cell division, it was found in the cytoplasm. To confirm the cellula r localization seen with the N-terminal tagged protein, we developed and pu rified peptide-specific antibodies. One of these antibodies (NCI 624), whic h recognizes a domain (aa 383-395) of menin, was used in immunofluorescence studies to corroborate the N-terminal tagging results. Further confirmatio n of menin localization was obtained in a pituitary tumor cell line derived from a familial MEN1 patient, which contained a mixed cell population with either none, or one functional copy of the MEN1 gene. Our results indicate that menin functions principally as a nuclear protein but may be found in the cytoplasm during cell division.