DROSOPHILA NF2/MERLIN HOMOLOGUE

神经纤维瘤病-2(NF2)是一种显性遗传性遗传病 以良性、生长缓慢的肿瘤的形成为特征的疾病 中枢神经系统。NF2抑癌基因编码 4.1超家族中的一个新成员，名叫梅林。4.1%的蛋白质 超家族通常被认为组织内部的功能域 通过将跨膜蛋白与细胞膜上的 潜在的细胞骨架或细胞质效应器。而当 Merlin被鉴定为蛋白4.1超家族的成员 引起了极大的兴趣，但它并没有导致一个具体的假设 关于它的细胞功能或它在肿瘤抑制中的作用。 在过去的两年里，我用 遗传和分子方法的组合，从而定义 蛋白质内的功能区。此外，我还发起了 用于识别与基因相互作用的基因的基因筛查 我设计的梅林的显性否定形式。的目标是 这项调查的最后一年将是克隆和描述 参与基于Merlin基因调控的几个新的基因座 扩散。

Neurofibromatosis type-2 (NF2) is a dominantly inherited genetic disorder characterized by the formation of benign, slow growing tumors of the central nervous system. The NF2 tumor suppressor gene encodes a novel member of the 4.1 superfamily called Merlin. Proteins of the 4.1 superfamily are generally believed to organize function domains within the plasma membrane by linking transmembrane proteins with the underlying cytoskeleton or cytosolic effectors. While the identification of Merlin as a member of the protein 4.1 superfamily has been of great interest, it has not led to a specific hypothesis regarding its cellular function or its role in tumor suppression. During the past two years, I have characterized the Merlin protein using a combination of genetic and molecular approaches, thereby defining functional regions within the protein. In addition, I have initiated a genetic screen to identify genes that interact genetically with a dominant negative form of Merlin that I have engineered. The goal for the last year of this investigation will be to clone and characterize several novel loci that are involved in Merlin based regulation of proliferation.