Relating protein interaction networks to physiology by systematic mutant analyses

通过系统突变分析将蛋白质相互作用网络与生理学联系起来

基本信息

  • 批准号:
    10649444
  • 负责人:
  • 金额:
    $ 35.18万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2015
  • 资助国家:
    美国
  • 起止时间:
    2015-02-01 至 2024-06-30
  • 项目状态:
    已结题

项目摘要

Hsp90 is an essential eukaryotic chaperone that helps to produce and maintain the active state of a select set of substrates or clients that are disproportionately linked to signaling processes including many that promote cancer and the emergence of drug resistance in fungi. For these reasons, inhibitor strategies to manipulate the Hsp90 chaperone system promise many potential therapeutic benefits. Inhibitors targeting the ATPase site of Hsp90 effectively limit the emergence of drug resistance in fungi and show promise as anti-cancer agents. However, ATPase inhibitors block all known functions of Hsp90, leading to undesirable side effects. In our previous work, we generated a comprehensive library of all possible mutations at each of the 709 positions in Hsp90 and quantified the effects of each variant on yeast growth rate as a readout of overall network function integrated over all client proteins. We will build on this work to investigate Hsp90-client interaction mechanism. We will determine how four specific clients are impacted by Hsp90 mutations, which will identify sites on Hsp90 that could be targeted to inhibit specific clients. We will perform deep mutational scanning on specific client proteins to identify the biophysical features that determine Hsp90 dependence. In addition, we have developed a novel approach to quantify the dominant effects of Hsp90 mutations, which we are using as a powerful new route to understand its mechanism of action. Our studies will provide important mechanistic insights into a protein-protein interaction network that is biologically and medically important.
Hsp90是一种重要的真核伴侣蛋白,有助于产生和维持活性状态

项目成果

期刊论文数量(13)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Systematic profiling of dominant ubiquitin variants reveals key functional nodes contributing to evolutionary selection.
对主要泛素变体的系统分析揭示了有助于进化选择的关键功能节点。
  • DOI:
    10.1016/j.celrep.2023.113064
  • 发表时间:
    2023
  • 期刊:
  • 影响因子:
    8.8
  • 作者:
    Padhy,AmritaArpita;Mavor,David;Sahoo,Subhashree;Bolon,DanielNA;Mishra,Parul
  • 通讯作者:
    Mishra,Parul
Mutational fitness landscape and drug resistance.
突变适应度景观和耐药性。
  • DOI:
    10.1016/j.sbi.2022.102525
  • 发表时间:
    2023
  • 期刊:
  • 影响因子:
    6.8
  • 作者:
    Flynn,Julia;Samant,Neha;Schneider-Nachum,Gily;Tenzin,Tsepal;Bolon,DanielNA
  • 通讯作者:
    Bolon,DanielNA
Saturation Mutagenesis of the HIV-1 Envelope CD4 Binding Loop Reveals Residues Controlling Distinct Trimer Conformations.
  • DOI:
    10.1371/journal.ppat.1005988
  • 发表时间:
    2016-11
  • 期刊:
  • 影响因子:
    6.7
  • 作者:
    Duenas-Decamp M;Jiang L;Bolon D;Clapham PR
  • 通讯作者:
    Clapham PR
Sequence dependencies and biophysical features both govern cleavage of diverse cut-sites by HIV protease.
序列依赖性和生物物理特征都控制着 HIV 蛋白酶对不同切割位点的切割。
Dominant negative mutations in yeast Hsp90 reveal triage decision mechanism targeting client proteins for degradation.
酵母 Hsp90 的显性负突变揭示了针对客户蛋白降解的分类决策机制。
{{ 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 }}

DANIEL N BOLON其他文献

DANIEL N BOLON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('DANIEL N BOLON', 18)}}的其他基金

Comprehensive analysis of fitness effects and epistasis along a billion-year evolutionary trajectory
十亿年进化轨迹上的适应度效应和上位性综合分析
  • 批准号:
    10212033
  • 财政年份:
    2021
  • 资助金额:
    $ 35.18万
  • 项目类别:
Comprehensive analysis of fitness effects and epistasis along a billion-year evolutionary trajectory
十亿年进化轨迹上的适应度效应和上位性综合分析
  • 批准号:
    10412075
  • 财政年份:
    2021
  • 资助金额:
    $ 35.18万
  • 项目类别:
Investigating structure activity relationships in autoprocessing by HIV-1 protease
研究 HIV-1 蛋白酶自动加工中的结构活性关系
  • 批准号:
    10258023
  • 财政年份:
    2021
  • 资助金额:
    $ 35.18万
  • 项目类别:
Comprehensive analysis of fitness effects and epistasis along a billion-year evolutionary trajectory
十亿年进化轨迹上的适应度效应和上位性综合分析
  • 批准号:
    10643977
  • 财政年份:
    2021
  • 资助金额:
    $ 35.18万
  • 项目类别:
Investigating structure activity relationships in autoprocessing by HIV-1 protease
研究 HIV-1 蛋白酶自动加工中的结构活性关系
  • 批准号:
    10374940
  • 财政年份:
    2021
  • 资助金额:
    $ 35.18万
  • 项目类别:
Relating protein interaction networks to physiology by systematic mutant analyses
通过系统突变分析将蛋白质相互作用网络与生理学联系起来
  • 批准号:
    8991326
  • 财政年份:
    2015
  • 资助金额:
    $ 35.18万
  • 项目类别:
Relating protein interaction networks to physiology by systematic mutant analyses
通过系统突变分析将蛋白质相互作用网络与生理学联系起来
  • 批准号:
    10436865
  • 财政年份:
    2015
  • 资助金额:
    $ 35.18万
  • 项目类别:
Relating protein interaction networks to physiology by systematic mutant analyses
通过系统突变分析将蛋白质相互作用网络与生理学联系起来
  • 批准号:
    10224929
  • 财政年份:
    2015
  • 资助金额:
    $ 35.18万
  • 项目类别:
Functional effects of all possible point mutations in oncogenes
癌基因中所有可能的点突变的功能影响
  • 批准号:
    8638362
  • 财政年份:
    2013
  • 资助金额:
    $ 35.18万
  • 项目类别:
Functional effects of all possible point mutations in oncogenes
癌基因中所有可能的点突变的功能影响
  • 批准号:
    8775634
  • 财政年份:
    2013
  • 资助金额:
    $ 35.18万
  • 项目类别:

相似海外基金

Delays in Acquisition of Oral Antineoplastic Agents
口服抗肿瘤药物的获取延迟
  • 批准号:
    9975367
  • 财政年份:
    2020
  • 资助金额:
    $ 35.18万
  • 项目类别:
Eliminate the difficulty of venous puncture in patients receiving antineoplastic agents - Development of a new strategy for the prevention of induration-
消除接受抗肿瘤药物的患者静脉穿刺的困难 - 制定预防硬结的新策略 -
  • 批准号:
    16K11932
  • 财政年份:
    2016
  • 资助金额:
    $ 35.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Molecular mechanisms of the antineoplastic agents inhibiting DNA replication and their applications to cancer patient treatmen
抗肿瘤药物抑制DNA复制的分子机制及其在癌症患者治疗中的应用
  • 批准号:
    19591274
  • 财政年份:
    2007
  • 资助金额:
    $ 35.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
PNET EXPERIMENTAL THERAPEUTICS--ANTINEOPLASTIC AGENTS AND TREATMENT DELIVERY
PNET 实验治疗——抗肿瘤药物和治疗实施
  • 批准号:
    6346309
  • 财政年份:
    2000
  • 资助金额:
    $ 35.18万
  • 项目类别:
TRAINING IN PHARMACOLOGY OF ANTINEOPLASTIC AGENTS
抗肿瘤药物药理学培训
  • 批准号:
    2720213
  • 财政年份:
    1999
  • 资助金额:
    $ 35.18万
  • 项目类别:
TRAINING IN PHARMACOLOGY OF ANTINEOPLASTIC AGENTS
抗肿瘤药物药理学培训
  • 批准号:
    6513197
  • 财政年份:
    1999
  • 资助金额:
    $ 35.18万
  • 项目类别:
Training in Pharmacology of Antineoplastic Agents
抗肿瘤药物药理学培训
  • 批准号:
    7101017
  • 财政年份:
    1999
  • 资助金额:
    $ 35.18万
  • 项目类别:
Training in Pharmacology of Antineoplastic Agents
抗肿瘤药物药理学培训
  • 批准号:
    6894842
  • 财政年份:
    1999
  • 资助金额:
    $ 35.18万
  • 项目类别:
TYROSINE KINASE INHIBITORS AS ANTINEOPLASTIC AGENTS
酪氨酸激酶抑制剂作为抗肿瘤剂
  • 批准号:
    2885074
  • 财政年份:
    1999
  • 资助金额:
    $ 35.18万
  • 项目类别:
TYROSINE KINASE INHIBITORS AS ANTINEOPLASTIC AGENTS
酪氨酸激酶抑制剂作为抗肿瘤剂
  • 批准号:
    6174221
  • 财政年份:
    1999
  • 资助金额:
    $ 35.18万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了