Quality Control: Selective Degradation From the ER/Golgi

质量控制:内质网/高尔基体的选择性降解

基本信息

  • 批准号:
    6898731
  • 负责人:
  • 金额:
    $ 25.78万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    1998
  • 资助国家:
    美国
  • 起止时间:
    1998-03-01 至 2007-05-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Soluble and membrane proteins of the secretory pathway enter the ER where they fold, are modified by carbohydrate addition and disulfide bond formation and assemble into complexes. Before exiting the ER, proteins must pass a quality control (ERQC) test. ERQC encompasses all those processes that ensure that only correctly folded/modified/assembled proteins exit the ER and includes retention in the ER, retrieval from downstream organelles and ER-associated degradation. ERQC contributes to the manifestation of disease either by depleting cells of essential proteins or by the toxic accumulation/aggregation of aberrant proteins. A progressive decline of ERQC in ageing highly differentiated neurons may play a major role in the neurodegenerative diseases such as Parkinson, Alzheimer's, Huntington's and prion diseases, all of which involve protein aggregation as the underlying pathology. The overall goal of this research is to understand the process of ERQC by defining the molecular components involved and determining how ERQC components function to recognize, retain, and retro-translocate misfolded substrates to be ubquitinated and degraded by the proteasome. The proposed project has four specific aims directed toward this goal. (1) The components of ERQC will be identified through a characterization of previously isolated ERQC mutants obtained at the end of the last grant period and through a genome wide mutant screen, synthetic genetic array analysis, synthetic lethal screen and micro array analysis to identify new components. (2) The role of ER to Golgi trafficking in ERQC will be examined through the use of retrograde trafficking mutants, cross-linking to Erv29p (a cargo receptor for ER exit) and determining the impact that glycosylation in the Golgi has on the degradation of ERQC substrates. (3) The aggregation of misfolded ERQC substrates in the ER results in their accumulation and associated cytotoxic effects. This specific aim is designed to identify ERQC substrate proteins that misfold and aggregate in the ER for use as a disease model in examining how cells contend with these potentially lethal accumulations. (4) A model substrate will assist in determining how soluble and polytopic membrane protein is treated differently by the ERQC. Knowledge and insights gained from these aims will lead to an understanding of the process of ERQC to be used to interpret protein aggregation based diseases.
描述(由申请人提供):分泌途径的可溶性蛋白和膜蛋白进入内质网,在那里折叠,通过碳水化合物添加和二硫键形成进行修饰并组装成复合物。在离开 ER 之前,蛋白质必须通过质量控制 (ERQC) 测试。 ERQC 涵盖确保只有正确折叠/修饰/组装的蛋白质离开 ER 的所有过程,包括保留在 ER 中、从下游细胞器中回收以及 ER 相关降解。 ERQC 通过消耗细胞必需蛋白质或通过异常蛋白质的毒性积累/聚集而导致疾病的表现。衰老的高度分化神经元中 ERQC 的逐渐下降可能在帕金森病、阿尔茨海默病、亨廷顿病和朊病毒病等神经退行性疾病中发挥重要作用,所有这些疾病都以蛋白质聚集为基础病理。本研究的总体目标是通过定义所涉及的分子成分并确定 ERQC 成分如何理解 ERQC 的过程 具有识别、保留和逆向易位错误折叠底物的功能,以被蛋白酶体泛素化和降解。拟议的项目有四个具体目标来实现这一目标。 (1) ERQC 的组成部分将通过对上次资助期结束时获得的先前分离的 ERQC 突变体进行表征,并通过全基因组突变体筛选、合成基因阵列分析、合成致死筛选和微阵列分析来鉴定新的成分。 (2) 将通过使用逆行运输突变体、与 Erv29p(ER 出口的货物受体)交联并确定高尔基体中的糖基化对 ERQC 降解的影响来检查 ER 对高尔基体运输的作用。 ERQC 基板。 (3) 错误折叠的 ERQC 底物在 ER 中的聚集导致其积累和相关的细胞毒性作用。这一具体目标旨在识别 ERQC 底物蛋白,这些蛋白在 ER 中错误折叠和聚集,用作疾病模型来检查细胞如何应对这些潜在致命的积累。 (4) 模型底物将有助于确定 ERQC 如何不同地处理可溶性膜蛋白和多胞膜蛋白。从这些目标中获得的知识和见解将有助于理解 ERQC 的过程,用于解释基于蛋白质聚集的疾病。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

ANTONY A COOPER其他文献

ANTONY A COOPER的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('ANTONY A COOPER', 18)}}的其他基金

QUALITY CONTROL--SELECTIVE PROTEIN DEGRADATION OF THE ER
质量控制--ER的选择性蛋白质降解
  • 批准号:
    6519819
  • 财政年份:
    1998
  • 资助金额:
    $ 25.78万
  • 项目类别:
QUALITY CONTROL--SELECTIVE PROTEIN DEGRADATION OF THE ER
质量控制--ER的选择性蛋白质降解
  • 批准号:
    6164818
  • 财政年份:
    1998
  • 资助金额:
    $ 25.78万
  • 项目类别:
Quality Control: Selective Degradation From the ER/Golgi
质量控制:内质网/高尔基体的选择性降解
  • 批准号:
    6740266
  • 财政年份:
    1998
  • 资助金额:
    $ 25.78万
  • 项目类别:
Quality Control: Selective Degradation From the ER/Golgi
质量控制:内质网/高尔基体的选择性降解
  • 批准号:
    6631390
  • 财政年份:
    1998
  • 资助金额:
    $ 25.78万
  • 项目类别:
QUALITY CONTROL--SELECTIVE PROTEIN DEGRADATION OF THE ER
质量控制--ER的选择性蛋白质降解
  • 批准号:
    2883064
  • 财政年份:
    1998
  • 资助金额:
    $ 25.78万
  • 项目类别:
QUALITY CONTROL--SELECTIVE PROTEIN DEGRADATION OF THE ER
质量控制--ER的选择性蛋白质降解
  • 批准号:
    6363285
  • 财政年份:
    1998
  • 资助金额:
    $ 25.78万
  • 项目类别:
QUALITY CONTROL--SELECTIVE PROTEIN DEGRADATION OF THE ER
质量控制--ER的选择性蛋白质降解
  • 批准号:
    2468920
  • 财政年份:
    1998
  • 资助金额:
    $ 25.78万
  • 项目类别:

相似海外基金

Characterization of a novel endosomal sorting complex
新型内体分选复合物的表征
  • 批准号:
    6998565
  • 财政年份:
    2005
  • 资助金额:
    $ 25.78万
  • 项目类别:
Characterization of a novel endosomal sorting complex
新型内体分选复合物的表征
  • 批准号:
    7123889
  • 财政年份:
    2005
  • 资助金额:
    $ 25.78万
  • 项目类别:
Quality Control: Selective Degradation From the ER/Golgi
质量控制:内质网/高尔基体的选择性降解
  • 批准号:
    6740266
  • 财政年份:
    1998
  • 资助金额:
    $ 25.78万
  • 项目类别:
Quality Control: Selective Degradation From the ER/Golgi
质量控制:内质网/高尔基体的选择性降解
  • 批准号:
    7072333
  • 财政年份:
    1998
  • 资助金额:
    $ 25.78万
  • 项目类别:
Quality Control: Selective Degradation From the ER/Golgi
质量控制:内质网/高尔基体的选择性降解
  • 批准号:
    6631390
  • 财政年份:
    1998
  • 资助金额:
    $ 25.78万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了