Characterization of the lethal (1)discs large-1 Oncogene of Drosophila

果蝇致死性 (1)discs large-1 癌基因的表征

• 批准号: 8917449
• 负责人: Peter Bryant
• 金额: $ 27.9万
• 依托单位: University of California-Irvine
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-02-01 至 1993-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=8917449&HistoricalAwards=false
• 关键词: Characterization; lethal; discs; large; Oncogene

Dr. Bryant proposes to continue his analysis of the lethal(1)discs large-1 (l(1)d.lg-1) locus, and oncogene of Drosophila melanogaster. Mutations in this locus cause neoplastic transformation of the imaginal tissue leading to an extended larval life and a block in pupariation. Other alleles allow normal imaginal growth but interfere with differentiation during metamorphosis. His initial genetic and molecular characterization of the locus has revealed the presence of at least three complementation groups and a complex pattern of expression of the l(1)d.lg-1 transcripts. Sequencing of partial cDNAs indicates that the locus encodes at least two different peptides, one of which appears to be transmembrane. Database homology searches have shown that the predicted l(1)d.lg-1 proteins contain the src homology region 3 or A-box. This amino acid motif has been found in several of the vertebrate oncogenes and can regulate the transforming ability of these proteins. Dr. Bryant plans to isolate full length cDNAs for the l(1)d.lg-1 transcripts to determine the sequence of the entire protein. He will also use these cDNAs to make minigene transformation constructs to correlate the genetic and molecular results. He will make antibodies to each of the predicted peptides to use for localization and biochemical characterization. Finally he will attempt to analyze the function of the A-box by sequencing this region from the pre-existing alleles of l(1)d.lg-1 and by creating specific alterations in this domain using in vitro mutagenesis. The results from these experiments should reveal how mutations in the l(1)d.lg-1 oncogene can cause neoplastic transformation and should help clarify the relationship of this gene to the vertebrate oncogenes. %%% This study will yield information about the regulation of a gene involved in growth control during development in Drosophila. This gene has homologies to mammalian genes involved in the transformation to malignant growth.

布莱恩特博士建议继续分析 致死（1）盘大-1（l（1）d.lg-1）基因座，以及 果蝇该位点的突变导致肿瘤性 成虫组织的转变导致了扩展 幼虫寿命和蛹期阻滞。其他等位基因允许 正常的成虫生长，但干扰分化过程中 变态他最初的基因和分子特征 发现至少有三个 互补组和复杂的表达模式， l（1）d.lg-1转录本。部分cDNA测序表明 该基因座编码至少两种不同的肽， 似乎是跨膜的数据库同源性检索 已经表明预测的l（1）d.lg-1蛋白含有src 同源区3或A盒。这个氨基酸基序已经被发现 在几种脊椎动物的致癌基因中， 这些蛋白质的转化能力。布莱恩特博士计划 分离l（1）d.lg-1转录物的全长cDNA， 确定整个蛋白质的序列。他也会用 这些cDNA，使微基因转化构建体， 将基因和分子结果联系起来他会让 针对每种预测肽的抗体，以用于 定位和生化表征。最后他会 试图通过对这个序列的排序来分析A盒的功能， 来自l（1）d.lg-1的预先存在的等位基因的区域， 用体外方法在这个结构域中产生特异性改变 诱变这些实验的结果应该揭示了 lg-1癌基因的突变可引起肿瘤 转变，并应有助于澄清这种关系 基因与脊椎动物癌基因的关系。 %%% 这项研究将提供有关基因调控的信息， 参与果蝇发育过程中的生长控制。这 基因与哺乳动物的基因具有同源性， 转化为恶性生长。