POSITIONAL CLONING OF MEN1 GENE

我们已经证明， MEN1基因使个体易患多种内分泌疾病 肿瘤1型（MEN1），以多发性肿瘤为特征， 甲状旁腺、胃肠道（GI）内分泌和垂体前叶 组织中MEN1编码蛋白的氨基酸序列 （menin）没有提供关于其功能的线索。我们已经表明 menin主要位于细胞核中， 独立核定位信号（NLS），位于 C-末端四分之一的蛋白质，已被鉴定。为了 了解menin的功能作用， 是通过同源重组产生的也 已经分离出menin基因的斑马鱼同源物，其作用 在斑马鱼胚胎发育中的作用。此外，本发明还提供了一种方法， menin与其他细胞蛋白的潜在相互作用正在被研究， 通过酵母双杂交系统、免疫沉淀和 GST menin pull-down测定。­表征 相互作用的蛋白质。

We have shown that inherited mutations in the MEN1 gene predispose individuals to develop multiple endocrine neoplasia type 1 (MEN1), characterized by multiple tumors of the parathyroid, gastrointestinal (GI) endocrine, and anterior pituitary tissues. The amino acid sequence of the MEN1 encoded protein (menin) does not provide clues as to its function. We have shown that menin is located primarily in the nucleus, and two functionally independent nuclear localization signals (NLS), located in the C-terminal quarter of the protein, have been identified. In order to understand the functional role of menin, a mouse knock-out model is being generated by homologous recombination. Also the zebrafish homolog of the menin gene has been isolated and its role in zebrafish embryonic development is being studied. In addition, potential interactions of menin with other cellular proteins are being investigated by yeast two- hybrid system, immunoprecipitation and GST­menin pull-down assays. Characterization of the interacting proteins is in progress.