POSITIONAL CLONING OF MEN1 GENE

我们发现MEN 1基因的遗传性突变使个体易患多发性内分泌瘤1型（MEN 1），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。我们已经表明，MEN 1编码的蛋白质（menin）主要位于细胞核中，它与AP 1家族转录因子的成员JunD相互作用。menin-JunD相互作用导致JunD诱导的转录的抑制，并且已经鉴定了参与其相互作用的蛋白质结构域。此外，潜在的相互作用menin与其他细胞蛋白正在研究酵母双杂交系统，免疫共沉淀和GST？menin pull-down测定。已经鉴定了来自小鼠、斑马鱼和果蝇的MEN 1同源基因。为了了解menin的功能作用，正在通过同源重组产生小鼠敲除模型，使用cre-lox系统以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