REGULATION AND FUNCTION OF HEAT SHOCK FACTORS IN TESTIS

睾丸热休克因子的调节及功能

基本信息

  • 批准号:
    2204889
  • 负责人:
  • 金额:
    $ 10.42万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    1995
  • 资助国家:
    美国
  • 起止时间:
    1995-07-01 至 2000-06-30
  • 项目状态:
    已结题

项目摘要

Spermatogenesis is the process by which immature male germ cells, through a complex series of events involving mitosis, meiosis, and differentiation of distinct spermatogenic cell types, are transformed into mature spermatozoa capable of fertilizing an ovum. Each spermatogenic cell type displays unique patterns of gene expression which ensure the production of proteins important for the specialized functions of these cells. The long- term goals of this project are to elucidate the mechanisms which regulate gene expression in spermatogenic cells and to understand the functions of regulated gene products in these cells. As a means to realize these goals, we propose to study the expression of Heat Shock Transcription Factor 2 (HSF2) in spermatogenic cells and its function in regulating hsp gene expression in these cells. Previous studies indicate that expression of several members of the hsp70 and hsp90 gene families (hsp70.2, hsc70t, hsp86) is regulated in spermatogenic cells, and that the promoters of these genes contain heat Shock Elements (HSEs), the HSF2 recognition sequence. Our previous studies demonstrate that HSF2 expression is regulated in germ cells, that the HSF2 protein exhibits constitutive DNA-binding activity in testis, and that HSF2 interacts with sequences in the hsp70.2 gene promoter. The hypothesis to be tested is that HSF2 expression and activity is regulated in germ cells to control hsp gene expression. We propose to precisely define the spatial and temporal patterns of HSF2 mRNA expression in testis and identify the mechanism which regulates HSF2 mRNA levels in testis cell types. HSF2 function in regulating gene expression in germ cells will be explored by determining the correlation between cellular localization of active HSF2 protein and hsp gene expression , by examining HSF2 interactions with hsp gene promoter sequences, both in vivo and in vitro, and by inhibiting HSF2 expression in germ cells and measuring resulting alterations in hsp gene expression. A second, related hypothesis to be tested is that the cellular stress response, which is mediated by Heat Shock Transcription Factor 1 (HSF1) and functions to protect cells from harmful effects of elevated temperature on cellular proteins, is involved in the well-known inhibitory effects of heat o spermatogenesis . This occurs either because spermatogenic cells lack the stress response and so are sensitive to heat-induced loss of protein function, or because stress response induction disrupts normal patterns of gene expression, thus interfering with essential cellular functions. To test this hypothesis, the stress-responsiveness of spermatogenic cells will be measured using probes for the three major parameters of the stress response; HSF1 DNA-binding activity, hsp70 mRNA, and hsp70 protein. The proposed studies will increase our understanding of the mechanisms of gene regulation in spermatogenic cells and of the importance of regulated gene expression for the specialized functions of these cells, and will also contribute to our understanding of how elevated temperature inhibits spermatogenesis. This information will provide a framework for exploring disease processes which affect spermatogenesis, and for development of new male contraceptives.
精子发生是未成熟的雄性生殖细胞通过 涉及有丝分裂、减数分裂和分化的一系列复杂事件 不同类型的生精细胞转化为成熟的 能够使卵子受精的精子。每种生精细胞类型 显示独特的基因表达模式,确保生产 对这些细胞的特殊功能很重要的蛋白质。长的- 这个项目的学期目标是阐明调节 生精细胞基因表达及其功能的研究 这些细胞中受调控的基因产物。作为实现这些目标的手段, 我们建议研究热休克转录因子2的表达 生精细胞中的热休克蛋白2及其在热休克蛋白基因调控中的作用 在这些细胞中表达。先前的研究表明, HSP70和HSP90基因家族的几个成员(hsp70.2,hsc70t, Hsp86)在生精细胞中受到调控,而这些基因的启动子 基因含有热休克元件(HSE),即HSF2识别序列。 我们以前的研究表明,HSF2在胚胎中的表达是受调控的 HSF2蛋白在细胞中表现出结构性DNA结合活性 睾丸,HSF2与hsp70.2基因中的序列相互作用 推动者。需要检验的假设是HSF2的表达和活性 在生殖细胞中被调节以控制HSP基因的表达。我们建议 精确定义HSF2基因表达的空间和时间模式 并确定其调控HSF2基因表达的机制。 睾丸细胞类型。热休克蛋白2在胚胎基因表达调控中的作用 将通过确定细胞与细胞之间的相关性来探索细胞 HSF2活性蛋白和HSP基因表达的定位 HSF2与HSP基因启动子序列在体内和体内的相互作用 体外,并通过抑制生殖细胞中HSF2的表达和测量 导致热休克蛋白基因表达的改变。 第二个需要检验的相关假设是,细胞压力 由热休克转录因子1(HSF1)和 保护细胞免受高温对其有害影响的功能 细胞蛋白质,参与了众所周知的热的抑制效应 没有精子发生。发生这种情况要么是因为生精细胞缺乏 应激反应和SO对热诱导的蛋白质损失很敏感 功能,或者因为应激反应诱导扰乱了正常的 基因表达,从而干扰基本的细胞功能。至 测试这一假设,生精细胞的应激反应将 使用探头测量应力的三个主要参数 反应:HSF1DNA结合活性、HSP70mRNA和HSP70蛋白。这个 提出的研究将增加我们对基因机制的理解。 生精细胞的调控及调控基因的重要性 表达这些细胞的特殊功能,还将 有助于我们理解高温如何抑制 精子发生。这些信息将为研究提供一个框架 影响精子发生的疾病过程,以及新的 男性避孕药。

项目成果

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Kevin D Sarge其他文献

Kevin D Sarge的其他文献

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{{ truncateString('Kevin D Sarge', 18)}}的其他基金

Regulation of HSF1 and HSF2 by SUMO-1 Modification
SUMO-1 修饰对 HSF1 和 HSF2 的调节
  • 批准号:
    6927166
  • 财政年份:
    2003
  • 资助金额:
    $ 10.42万
  • 项目类别:
Regulation of HSF1 and HSF2 by SUMO-1 Modification
SUMO-1 修饰对 HSF1 和 HSF2 的调节
  • 批准号:
    6680538
  • 财政年份:
    2003
  • 资助金额:
    $ 10.42万
  • 项目类别:
Regulation of HSF1 and HSF2 by SUMO-1 Modification
SUMO-1 修饰对 HSF1 和 HSF2 的调节
  • 批准号:
    6784174
  • 财政年份:
    2003
  • 资助金额:
    $ 10.42万
  • 项目类别:
Regulation of HSF1 and HSF2 by SUMO-1 Modification
SUMO-1 修饰对 HSF1 和 HSF2 的调节
  • 批准号:
    7271321
  • 财政年份:
    2003
  • 资助金额:
    $ 10.42万
  • 项目类别:
REGULATION OF PROTEIN PHOSPHATASE 2A BY CELLULAR PROTEIN
细胞蛋白对蛋白磷酸酶 2A 的调节
  • 批准号:
    6700760
  • 财政年份:
    2001
  • 资助金额:
    $ 10.42万
  • 项目类别:
REGULATION OF PROTEIN PHOSPHATASE 2A BY CELLULAR PROTEIN
细胞蛋白对蛋白磷酸酶 2A 的调节
  • 批准号:
    6628915
  • 财政年份:
    2001
  • 资助金额:
    $ 10.42万
  • 项目类别:
REGULATION OF PROTEIN PHOSPHATASE 2A BY CELLULAR PROTEIN
细胞蛋白对蛋白磷酸酶 2A 的调节
  • 批准号:
    6286506
  • 财政年份:
    2001
  • 资助金额:
    $ 10.42万
  • 项目类别:
REGULATION OF PROTEIN PHOSPHATASE 2A BY CELLULAR PROTEIN
细胞蛋白对蛋白磷酸酶 2A 的调节
  • 批准号:
    6498841
  • 财政年份:
    2001
  • 资助金额:
    $ 10.42万
  • 项目类别:
REGULATION AND FUNCTION OF HEAT SHOCK FACTORS IN TESTIS
睾丸热休克因子的调节及功能
  • 批准号:
    2889120
  • 财政年份:
    1995
  • 资助金额:
    $ 10.42万
  • 项目类别:
REGULATION AND FUNCTION OF HEAT SHOCK FACTORS IN TESTIS
睾丸热休克因子的调节及功能
  • 批准号:
    2403406
  • 财政年份:
    1995
  • 资助金额:
    $ 10.42万
  • 项目类别:

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  • 批准号:
    147394-1992
  • 财政年份:
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