课题基金 / 基金详情

SPECIFICITY OF UBIQUITINATION--THE HPV E6/E6 AP PARADIGM

SPECIFICITY OF UBIQUITINATION--THE HPV E6/E6 AP PARADIGM
泛素化的特异性——HPV E6/E6 AP 范式
批准号:
2010998
负责人:
JON HUIBREGTSE
金额:
$21.4万
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:
1996-12-13 至 2001-11-30

项目摘要

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相关文献

中文摘要
翻译
描述:E6-AP(E6相关蛋白)是一种细胞蛋白, 在E6依赖性细胞凋亡中与p53的泛素化相关并催化p53的泛素化。 方式 E6-AP的表征显示其代表了大的 泛素蛋白连接酶(或E3蛋白)家族,已被 假定在底物选择性中起主要作用。 申请人 提出了E6-AP相关E3蛋白的功能模型, 它们由两个广泛的结构域组成:N-末端底物识别 结构域和C-末端催化结构域(hect结构域,用于同源 至E6-AP C-末端),其泛素化结合的底物。 具体 本建议的目的是:1)通过确定是否 底物特异性可以通过N-末端取代 如果hect结构域在E3之间是功能上可互换的, 蛋白质,2)通过精确地测定E6-AP来评估该模型, 定位p53结合和hect结构域所需的决定因素 功能,和3)鉴定Rsp 5的底物,一种必需的酵母hectE 3, 从2域模型的预测开始, 遗传和生物化学方法。 这一长期目标 应用的目的是了解hect E3的作用机制 蛋白质及其作用,以及高危HPV E6的作用 蛋白质(和可能的细胞类似物),在指导特异性 泛素系统 最终目标是更全面地了解 HPV相关的致癌作用和蛋白质调控的其他过程 泛素化
英文摘要
DESCRIPTION: E6-AP (E6-Associated Protein) is a cellular protein that associates with and catalyzes ubiquitination of p53 in anE6-dependent manner. Characterization of E6-AP showed it to be representative of a large family of ubiquitin-protein ligases (or E3 proteins), which have been postulated to play the major role in substrate selectivity. The applicant proposes a model for function of the E6-AP-related E3 proteins which states that they consist of two broad domains: an N-terminal substrate recognition domain, and a C-terminal catalytic domain (the hect domain, for homologous to E6-AP C-terminus) which ubiquitinates bound substrates. The specific aims of this proposal are: 1) to evaluate this model by determining if substrate specificity can be redirected by substitution of N-terminal sequences and if hect domains are functionally interchangeable among E3 proteins, 2) to evaluate this model with respect to E6-AP by precisely mapping the determinants necessary for p53 association and hect domain function, and 3) to identify substrates of Rsp5, an essential yeast hectE3, beginning with predictions of the 2-domain model and taking a combined genetic and biochemical approach. The long-term objectives of this application are to understand the mechanisms of action of the hect E3 proteins and their role, as well as the role of the high-risk HPV E6 proteins (and possible cellular analogs), in directing the specificity of the ubiquitin system. The ultimate goal is a more complete understanding of HPV-associated carcinogenesis and other processes regulated by protein ubiquitination.
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FASEB SRC on Ubiquitin and Cellular Regulation
Mechanism and Function of ISG15
  • 批准号:
    9176962
  • 项目类别:
  • 资助金额:
    $38.41万
  • 财政年份:
    2011
  • 负责人:
    JON HUIBREGTSE
  • 依托单位:
Mechanism and Function of ISG15 Conjugation
  • 批准号:
    8258706
  • 项目类别:
  • 资助金额:
    $33.19万
  • 财政年份:
    2011
  • 负责人:
    JON HUIBREGTSE
  • 依托单位:
Mechanism and Function of ISG15 Conjugation
  • 批准号:
    8459502
  • 项目类别:
  • 资助金额:
    $31.26万
  • 财政年份:
    2011
  • 负责人:
    JON HUIBREGTSE
  • 依托单位: