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

MEN1基因是一种经定位鉴定的肿瘤抑制基因 由包括MDB成员在内的NIH合作小组进行克隆。生殖系 在受影响的MEN1家族受试者中发现了该基因的突变， 该基因的体细胞突变已在散发性 内分泌和其他肿瘤。该基因编码610个残基蛋白。 称为薄荷素，与其他已知蛋白质没有同源性，也没有 明显的功能图案。我们已经启动了一系列研究，旨在 在定义结构、功能、亚细胞定位和范围方面 脑薄荷素的表达。我们已经产生了一系列多克隆多肽 已证明在免疫印迹和免疫沉淀中有用的抗血清 学习。此外，这些抗体还检测到 用于结构和生化的重组薄荷素形式 分析表明，编码薄荷素的基因已在293中瞬时转导 亚细胞后用于监测其表达的细胞和抗体 分馏法。这些研究将扩展到突变形式的 蛋白。目前还在努力识别生物化学 与薄荷素相关的活动，并定义mRNA和/或变化 蛋白质在各种条件下在细胞和组织中的表达， 例如，内分泌过度增生的状态。

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.