POSITIONAL CLONING OF MEN1 GENE

我们已经证明，MEN1基因的遗传突变使个体容易患上多发性内分泌腺瘤病1型(MEN1)，其特征是甲状旁腺、胃肠道(GI)内分泌和垂体前叶组织的多发性肿瘤。我们已经证明MEN1编码的蛋白(Menin)主要位于细胞核中，它与AP1家族转录因子中的成员Jund相互作用。Menin-Jund相互作用导致抑制Jund诱导的转录，并确定了参与它们相互作用的蛋白质结构域。此外，薄荷素与其他细胞蛋白的潜在相互作用正在通过酵母双杂交系统、免疫共沉淀和GST？薄荷素下拉试验进行研究。已经从小鼠、斑马鱼和果蝇中鉴定出MEN1同源基因。为了了解脑膜素的功能作用，正在通过同源重组产生一个小鼠基因敲除模型，使用cre-lox系统来允许组织特异性失活。-癌症研究

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. We have shown that the MEN1 encoded protein (menin) is located primarily in the nucleus, and it interacts with JunD, a member of the AP1 family transcription factors. The menin-JunD interaction results in the repression of JunD- induced transcription, and the protein domains involved in their interaction have been identified. Also, potential interactions of menin with other cellular proteins are being investigated by the yeast two- hybrid system, co-immunoprecipitation and GST?menin pull-down assays. MEN1 homologous genes from mouse, zebrafish and Drosophila have been identified. In order to understand the functional role of menin, a mouse knockout model is being generated by homologous recombination, using the cre-lox system to allow tissue specific inactivation. - Cancer Research