Menin, a gene product responsible for multiple endocrine neoplasia type 1, interacts with the putative tumor metastasis suppressor nm23.
Menin, a gene product responsible for multiple endocrine neoplasia type 1, interacts with the putative tumor metastasis suppressor nm23.
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DOI：
10.1006/bbrc.2001.4723
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发表时间：
2001-04
影响因子：
3.1
通讯作者：
N. Ohkura;Mari Kishi;Toshihiko Tsukada;Ken Yamaguchi
中科院分区：
文献类型：
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作者：
N. Ohkura;Mari Kishi;Toshihiko Tsukada;Ken Yamaguchi
尽管导致 1 型多发性内分泌肿瘤 (MEN1) 的基因已被鉴定，但其基因产物 menin 的功能尚不清楚。为了检查 MEN1 基因的生物学作用，我们使用 MEN1 cDNA 片段作为诱饵，通过酵母双杂交系统寻找相关蛋白。在筛选第 17 天的大鼠胎儿脑胚胎文库时，检测到高水平的 MEN1 表达，我们鉴定出一种假定的肿瘤转移抑制因子 nm23/核苷二磷酸 (NDP) 激酶作为相关蛋白。基于谷胱甘肽 S-转移酶下拉实验的体外相互作用测定证实了这一发现。这种关联需要几乎整个 menin 蛋白，并且在 MEN1 患者中报告的几种错义 MEN1 突变导致 nm23 结合活性丧失。这一结果表明，这种相互作用可能在 menin 蛋白的生物学功能中发挥重要作用，包括肿瘤抑制活性。
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.