TUMOR SUPPRESSORS AND CELL PROLIFERATION IN DROSOPHILA

果蝇的肿瘤抑制因子和细胞增殖

• 批准号: 6137562
• 负责人: TIAN XU
• 金额: $ 26万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-03-05 至 2000-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6137562
• 关键词: Drosophilidae; alleles; biological signal transduction; cell cycle; cell growth regulation; developmental genetics; gene interaction; gene mutation; genetically modified animals; molecular cloning; phenotype; site directed mutagenesis; tumor suppressor genes

Studies on the regulation of cell proliferation are important to our understanding of developmental biology and tumorigenesis. The long-term goal of the proposed research is to learn the molecular mechanisms that negatively regulate cell proliferation. In order to address this question, we are identifying growth-constraining tumor suppressor genes and studying their functions in the developing imaginal tissues of Drosophila melanogaster. Several aspects of this system make it uniquely suited for analyzing mechanisms that negatively regulate cell proliferation: (1) mechanisms are known to exist in controlling cell proliferation in imaginal tissues; (2) a newly developed genetic technique provides an unprecedented opportunity to identify mutations affecting such mechanisms in mosaic animals, and components of such mechanisms have already been identified; (3) additional components can be identified by future genetic screens; and (4) standard molecular and genetic techniques can be used to characterize these components. The three key genes to be studied are lats, "93B" and "2-1", in which recessive mutations can cause dramatic overproliferation of mutant cells in mosaic animals. The lats gene encodes a novel protein kinase homolog with a putative SH3-binding site. The specific aims of this proposal are: (1) to continue the molecular and genetic characterization of the lats, "93B", and "2-1" genes; and (2) to identify genetically and characterize additional genes involved in the negative regulation of cell proliferation or that interact with lats. The genetic screens will identify a network of genes involved in controlling cell proliferation during development. The genetic and molecular characterizations proposed will define the relationships among these genes and begin to assign biochemical functions which will aid in understanding their interactions at the molecular level. In this manner, we hope to learn how cell proliferation is regulated during normal development and how mutations could lead to abnormal growth and tumorigenesis.

研究细胞增殖的调控对我们的研究很重要。 了解发育生物学和肿瘤发生。长期 这项研究的目的是了解 负调节细胞增殖。为了解决这个问题， 我们正在鉴定抑制生长的肿瘤抑制基因， 它们在果蝇发育中的成虫组织中的功能 黑腹菌该系统的几个方面使其特别适合于 分析负调节细胞增殖的机制：（1） 已知存在控制细胞增殖的机制， （2）新开发的遗传技术提供了一种 前所未有的机会，以确定影响这种机制的突变 在嵌合体动物中，这种机制的组成部分已经被 （3）其他成分可以通过将来的遗传学鉴定 筛选;以及（4）标准分子和遗传技术可用于 描述这些组件。 待研究的三个关键基因是lats、“93 B”和“2-1”，其中 隐性突变可导致突变细胞的急剧过度增殖 在马赛克动物中。lats基因编码一种新的蛋白激酶同系物 有一个推测的SH 3结合位点这项建议的具体目标是： (1)为了继续LATS的分子和遗传表征， “93 B”和“2-1”基因;和（2）遗传鉴定和表征 参与细胞增殖负调控的其他基因 或与背阔肌相互作用。基因筛选将确定一个网络， 在发育过程中控制细胞增殖的基因。的 提出的遗传和分子特征将定义 这些基因之间的关系，并开始分配生化功能 这将有助于理解它们在分子水平上的相互作用。 通过这种方式，我们希望了解细胞增殖是如何调节的 以及突变如何导致异常生长 和肿瘤发生。