STRUCTURE ANS FUNCTION OF THE MEN1 GENE AND ITS PROTEIN PRODUCT, MENIN

MEN 1基因是一个肿瘤抑制基因，通过定位鉴定， 由包括MDB成员在内的NIH协作组进行克隆。种系 在MEN 1激酶受影响的受试者中发现该基因的突变， 该基因的体细胞突变已经在散发性 内分泌肿瘤和其他肿瘤。该基因编码610个残基的蛋白质 称为menin，与其他已知蛋白质没有同源性， 明显的功能性图案。我们已经启动了一系列研究， 在定义结构，功能，亚细胞定位，和范围， 男人的表情。我们已经产生了一系列多克隆肽 已证明可用于免疫印迹和免疫沉淀的抗血清 问题研究此外，这些抗体检测以下表达： 重组形式的menin用于结构和生物化学 已将编码menin的cDNA瞬时转染293个 细胞和抗体用于监测其表达后亚细胞 分馏这些研究将扩展到 蛋白同时也在努力鉴别生物化学物质 与menin相关的活动，并定义mRNA和/或 在各种条件下细胞和组织中的蛋白质表达， 例如内分泌增生状态。

The MEN1 gene is a tumor suppressor gene identified by positional cloning by an NIH collaborative group including members of MDB. Germline mutations in the gene are found in affected subjects of MEN1 kindreds, and somatic mutations in the gene have been identified in sporadic endocrine and other tumors. The gene encodes a 610 residue protein termed menin without homology to other known proteins and without obvious functional motifs. We have initiated a series of studies aimed at defining the structure, function, subcellular localization, and range of expression of menin. We have generated a series of polyclonal peptide antisera that have proved useful in immunoblot and immunoprecipitation studies. Furthermore,these antibodies detect the expression of recombinant forms of menin to be used for structural and biochemical analyses.The cDNA encoding menin has been transiently transfected in 293 cells and antibodies used to monitor its expression after subcellular fractionation. These studies will be extended to mutant forms of the protein. Efforts are also being directed at identifying biochemical activities associated with menin, and defining changes in mRNA and/or protein expression in cells and tissues under a variety of conditions, e.g. states of endocrine hyperplasia.