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FUNCTION OF MERLIN, A DROSOPHILA NF2 GENE HOMOLOGUE

FUNCTION OF MERLIN, A DROSOPHILA NF2 GENE HOMOLOGUE
果蝇 NF2 基因同源物 MERLIN 的功能
批准号:
6343860
负责人:
Richard G Fehon
金额:
$30.15万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1996
资助国家:
美国
项目状态:
已结题
起止时间:
1996-01-01 至 2003-12-31

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中文摘要
翻译
2 型神经纤维瘤病 (NF2) 是一种显性遗传性疾病,已被 被证明是由 Merlin (Schwannomin) 的突变引起的,Merlin 是 蛋白质4.1超家族。 NF2 的症状,通常在早期出现 成年后的生活,都是由双侧前庭的形成引起的 神经鞘瘤和其他良性肿瘤。 Merlin 和的细胞功能 其在肿瘤抑制中的作用仍然很大程度上未知。识别 特定蛋白质和信号转导途径与 Merlin 相互作用 尤其重要,因为这些伴侣可能充当遗传性伴侣 NF2 疾病表型的修饰因子并提供潜在靶标 治疗剂。常见的果蝇(果蝇)已被证明是一种 用于识别基因功能的遗传修饰剂的有用模型系统。 因此,该提案的总体目标是检查细胞 Merlin 和果蝇的功能,识别其所用的蛋白质 互动,并审视梅林与密切关系者之间的关系 相关的 Ezrin/Radixin/Moesin 蛋白。 在下一个资助期内,我们计划继续对Merlin的研究 在个体细胞中发育生物体中发挥作用。具体来说, 拟议的实验将: 1) 检查 Merlin 功能的调节机制 体外诱变和细胞及生化分析的结合 的蛋白质功能。 2) 通过筛选来识别 Merlin 功能的第二个位点修饰子 增强或抑制显性失活表型的突变 梅林转基因。 3)阐明ERM蛋白的功能及其功能 通过分离和表征突变与 Merlin 的关系 果蝇 Moesin 基因。 这些实验有望提供对功能的深入了解 Merlin 和 ERM 蛋白。因此,他们将为我们做出贡献 对人类 NF2、肿瘤抑制的总体了解,以及 致癌作用。此外,所提出的实验应该导致 更好地了解心尖发生的细胞过程 连接域。最后,这些研究应有助于以下方面的工作: 细胞相互作用控制细胞生长的机制 并决定发育过程中的细胞命运。
英文摘要
Neurofibromatosis type 2 (NF2), a dominantly inherited disease, has been shown to be caused by mutations in Merlin (Schwannomin), a member of the protein 4.1 superfamily. Symptoms of NF2, which usually appear by early adult life, are caused by the formation of bilateral vestibular Schwannomas and other benign tumors. The cellular functions of Merlin and its role in tumor suppression are still largely unknown. Identifying specific proteins and signal transduction pathways with Merlin interacts is especially important because these partners may act as genetic modifiers of NF2 disease phenotypes and provide potential targets for therapeutic agents. The common fruit fly, Drosophila, has proven to be a useful model system for identifying genetic modifiers of gene function. The overall goal of this proposal is therefore to examine the cellular functions of Merlin and Drosophila, identify the proteins with which it interacts, and examine the relationship between Merlin and the closely related Ezrin/Radixin/Moesin proteins. In the next funding period, we plan to continue our studies of Merlin function in developing organisms in individual cells. Specifically, the proposed experiments will: 1) Examine the mechanisms by which Merlin function is regulate using a combination of in vitro mutagenesis and cellular nad biochemical analysis of protein function. 2) Identify second site modifiers of Merlin function by screening for mutations that enhance or suppress the phenotypes of dominant-negative Merlin transgenes. 3) Elucidate the functions of ERM proteins and their functional relationship with Merlin by isolating and characterizing mutations in the Drosophila Moesin gene. These experiments are expected to provide insights into the functions of Merlin and the ERM proteins. Thus they will contribute to our understanding of human NF2, tumor suppression in general, and carcinogenesis. In addition, the proposed experiments should lead to a better understanding of cellular processes that occur in the apical junctional domain. Finally, these studies should contribute to work on the mechanisms by which cellular interactions function to control cell growth and determine cell fate during development.
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Function of NF2/Merlin in regulation of the Hippo/Salvador/Warts growth control pathway
  • 批准号:
    10826475
  • 项目类别:
  • 资助金额:
    $49.27万
  • 财政年份:
    2023
  • 负责人:
    Richard G Fehon
  • 依托单位:
Regulation of the Dachs core complex in tissue growth control
  • 批准号:
    10166884
  • 项目类别:
  • 资助金额:
    $34.02万
  • 财政年份:
    2019
  • 负责人:
    Richard G Fehon
  • 依托单位:
Regulation of the Dachs core complex in tissue growth control
  • 批准号:
    9803476
  • 项目类别:
  • 资助金额:
    $34.02万
  • 财政年份:
    2019
  • 负责人:
    Richard G Fehon
  • 依托单位:
Regulation of the Dachs core complex in tissue growth control
  • 批准号:
    10417216
  • 项目类别:
  • 资助金额:
    $34.02万
  • 财政年份:
    2019
  • 负责人:
    Richard G Fehon
  • 依托单位:
海外基金