Regular Article
Menin, a Gene Product Responsible for Multiple Endocrine Neoplasia Type 1, Interacts with the Putative Tumor Metastasis Suppressor nm23

https://doi.org/10.1006/bbrc.2001.4723Get rights and content

Abstract

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/nucleside 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.

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      Citation Excerpt :

      The MEN1 gene encodes a 610 amino acid protein named menin,4 which is mainly localised in the nucleus. Menin interacts with a number of proteins, incuding JunD,5 several members of nuclear factor-κB,6 Smad1, 3 and 5,7,8 nm23,9 RPA2,10 FancD2,11 ASK,12 MLL1 and MLL2.13–15 The fact that the majority of its protein partners are transcription factors and co-factors allows to hypothesise that menin could be involved in transcriptional regulation.

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