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MOLECULAR GENETICS OF C OXIDASE

MOLECULAR GENETICS OF C OXIDASE
C氧化酶的分子遗传学
批准号:
2185986
负责人:
LAWRENCE GROSSMAN
金额:
$17.51万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1993
资助国家:
美国
项目状态:
已结题
起止时间:
1993-02-01 至 1997-01-31

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中文摘要
翻译
细胞色素c氧化酶,电子传递的末端蛋白 链,在哺乳动物中由十三个亚基组成,其中三个由 线粒体DNA,其余部分为核DNA。 至少其中三个 这些核亚基以不止一种分子形式、异构体、 不同基因的产物。 拟议的实验将提供 对这些亚型的细胞功能的深入了解,这可能是 与个体发育和细胞生理学相关。 在 此外,同工型表达与人类神经肌肉 疾病。 该项目将重点关注两个亚基,COX VIIa 和 COX VIIc, 由三个基因编码。 COX7a 显示心脏和肌肉特异性 异构体基因,COX7a-H,已分离,以及异构体基因 COX7a-L 在所有组织中表达。 第三个基因 COX7c 似乎具有 在所有组织中都有单一的表达形式。 具体目标是(1) 分离并表征 COX7a-L 和 COX7c 基因,并比较 COX7a-H 的调控区域; (2) 构建报告者结构 每个基因通过删除和定义顺式作用调控元件 突变方法; (3)考察生理效应 同种型表达的调节条件; (4) 隔离和研究 反式作用调节因素。 第三个目标,研究监管 同种型表达,将通过两种方式进行:通过原位 异构体特异性探针与心脏区域的杂交 在非常不同的氧化应激下工作,并通过共转染 将可区分的报告构建体中的两种亚型基因导入细胞中 置于各种生理条件下。 这个项目适合 纳入推断核作用的长期目标 编码的亚基和用于调节氧化功能的机制, 并将这些知识应用于核基因的研究 线粒体疾病。
英文摘要
Cytochrome c oxidase, the terminal protein of the electron transport chain, is composed in mammals of thirteen subunits, three encoded by mitochondrial DNA and the remainder by nuclear DNA. At least three of these nuclear subunits occur in more than one molecular form, isoforms, the products of separate genes. The proposed experiments will provide insights into the cellular function of these isoforms, which may be related to both ontogenetic development and cellular physiology. In addition, isoform expression has been implicated in human neuromuscular disease. This project will focus on two subunits, COX VIIa and COX VIIc, encoded by three genes. COX7a displays a heart- and muscle-specific isoform gene, COX7a-H, which is already isolated, and an isoform gene expressed in all tissues, COX7a-L. A third gene, COX7c, appears to have a single expressed form in all tissues. The specific aims are to (1) isolate and characterize the COX7a-L and COX7c genes, and compare the regulatory regions to those of COX7a-H; (2) make reporter constructs of each gene to define cis-acting regulatory elements by deletional and mutational approaches; (3) investigate the effect of physiological conditions on regulation of isoform expression; and (4) isolate and study trans-acting regulatory factors. The third aim, studying regulation of isoform expression, will be pursued in two ways: by in situ hybridization of isoform-specific probes to regions of the heart that operate under very different oxidative stresses, and by cotransfection of both isoform genes in distinguishable reporter constructs into cells placed under a variety of physiological conditions. This project fits into the longer term objectives of deducing the role of the nuclear- encoded subunits and the mechanisms used to regulate oxidative function, and applying this knowledge to the study of nuclear genes in mitochondrial disease.
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MOLECULAR GENETICS OF MAMMALIAN CYTOCHROME C OXIDASE
MOLECULAR GENETICS OF MAMMALIAN CYTOCHROME C OXIDASE
  • 批准号:
    6179776
  • 项目类别:
  • 资助金额:
    $18.71万
  • 财政年份:
    1993
  • 负责人:
    LAWRENCE GROSSMAN
  • 依托单位:
MOLECULAR GENETICS OF MAMMALIAN CYTOCHROME C OXIDASE
  • 批准号:
    6018929
  • 项目类别:
  • 资助金额:
    $18.16万
  • 财政年份:
    1993
  • 负责人:
    LAWRENCE GROSSMAN
  • 依托单位:
MOLECULAR GENETICS OF MAMMALIAN CYTOCHROME OXIDASE
  • 批准号:
    3307978
  • 项目类别:
  • 资助金额:
    $16.51万
  • 财政年份:
    1993
  • 负责人:
    LAWRENCE GROSSMAN
  • 依托单位:
海外基金