Di-ubiquitin modification of ubiquitin ligase adaptors in membrane protein downregulation

泛素连接酶接头的双泛素修饰在膜蛋白下调中的作用

基本信息

  • 批准号:
    10521677
  • 负责人:
  • 金额:
    $ 41.07万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-08-01 至 2026-05-31
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY/ABSTRACT Post-translational modification by ubiquitin is an essential mechanism to alter protein function in eukaryotes. Ubiquitin, a 76 amino acid protein, is attached to specific proteins via a cascade of ubiquitin activating enzyme E1, conjugating enzyme E2, and ubiquitin ligase E3. Ubiquitination plays an essential role in a broad aspect of cellular processes, including transcription, DNA repair, signal transduction, autophagy, cell cycle, immune response, and membrane trafficking. Aberration in the ubiquitination system leads to a number of human diseases, such as neurodegenerative diseases and cancers. Within the ubiquitination cascade, E3s primarily dictate the specificity of the ubiquitination system and thus are often the focal points of research and attractive therapeutic targets. The Nedd4 family E3s are an essential family of HECT-type E3s, members of which contain an N-terminal C2 domain followed by 2-4 WW domains and the C-terminal HECT domain. Nedd4 E3s recognize substrates carrying a “PPxY” motif through their WW domains. However, most substrates lack such a motif but engage with the ligase through “PPxY” motif-containing adaptors. We recently discovered that in yeast, the ubiquitin E3 ligase adaptor protein Art1 is primed with di-ubiquitination and the attachment of the di-Ub chain to a specific lysine residue in Art1 is warranted for its full activity. In this proposal, we plan to investigate the physiological function of adaptor di-ubiquitination and to elucidate the molecular mechanisms of the modular ubiquitination platform form with Nedd4 E3 ligase and di-ubiquitinated adaptors. Specifically, we will pursue the following aims: Aim 1: To investigate the mechanism of Nedd4 E3 adaptor di-ubiquitination. Aim 2: To determine the role of di-ubiquitinated adaptor-E3 complexes in substrate ubiquitination. Aim 3: To elucidate the molecular architecture of di-ubiquitinated adaptors with the Nedd4 E3 ligases. Uncovering the physiological role of Need4 E3 adaptors di-ubiquitination will be of critical importance to understand the molecular basis of how E3 adaptors specifically recognize substrate proteins and efficiently present the substrates for ubiquitination by HECT E3 ligases. We expect the successful implementation of this proposal will not only make significant contributions to the understanding of the molecular mechanisms underlying the Nedd4 E3 ligase/adaptor mediated ubiquitination, but also shed light on the mechanism of protein quality control governed by targeted ubiquitination.
项目总结/文摘

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 }}

SCOTT D EMR其他文献

SCOTT D EMR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('SCOTT D EMR', 18)}}的其他基金

Di-ubiquitin modification of ubiquitin ligase adaptors in membrane protein downregulation
泛素连接酶接头的双泛素修饰在膜蛋白下调中的作用
  • 批准号:
    10669780
  • 财政年份:
    2022
  • 资助金额:
    $ 41.07万
  • 项目类别:
ROLE OF THE YEAST VPS15/VPS34 KINASE COMPLEX IN YEAST SECRETORY PROTEIN SORTING
酵母 VPS15/VPS34 激酶复合物在酵母分泌蛋白分选中的作用
  • 批准号:
    6585971
  • 财政年份:
    2002
  • 资助金额:
    $ 41.07万
  • 项目类别:
ROLE OF THE YEAST VPS15/VPS34 KINASE COMPLEX IN YEAST SECRETORY PROTEIN SORTING
酵母 VPS15/VPS34 激酶复合物在酵母分泌蛋白分选中的作用
  • 批准号:
    6448183
  • 财政年份:
    2001
  • 资助金额:
    $ 41.07万
  • 项目类别:
GORDON RESEARCH CONFERENCE ON LYSOSOMES
戈登溶酶体研究会议
  • 批准号:
    6158878
  • 财政年份:
    2000
  • 资助金额:
    $ 41.07万
  • 项目类别:
ROLE OF THE YEAST VPS15/VPS34 KINASE COMPLEX IN YEAST SECRETORY PROTEIN SORTING
酵母 VPS15/VPS34 激酶复合物在酵母分泌蛋白分选中的作用
  • 批准号:
    6314036
  • 财政年份:
    2000
  • 资助金额:
    $ 41.07万
  • 项目类别:
ROLE OF THE YEAST VPS15/VPS34 KINASE COMPLEX IN YEAST SECRETORY PROTEIN SORTING
酵母 VPS15/VPS34 激酶复合物在酵母分泌蛋白分选中的作用
  • 批准号:
    6102883
  • 财政年份:
    1999
  • 资助金额:
    $ 41.07万
  • 项目类别:
ROLE OF THE YEAST VPS15/VPS34 KINASE COMPLEX IN YEAST SECRETORY PROTEIN SORTING
酵母 VPS15/VPS34 激酶复合物在酵母分泌蛋白分选中的作用
  • 批准号:
    6269600
  • 财政年份:
    1998
  • 资助金额:
    $ 41.07万
  • 项目类别:
ROLE OF THE YEAST VPS15 PROTEIN KINASE IN INTRACELLULAR PROTEIN SORTING
酵母 VPS15 蛋白激酶在细胞内蛋白分选中的作用
  • 批准号:
    6237382
  • 财政年份:
    1997
  • 资助金额:
    $ 41.07万
  • 项目类别:
PROTEIN SORTING TO THE LYSOSOME-LIKE VACUOLE IN YEAST
酵母中溶酶体样液泡的蛋白质分类
  • 批准号:
    3281753
  • 财政年份:
    1983
  • 资助金额:
    $ 41.07万
  • 项目类别:
PROTEIN SORTING TO THE LYSOSOME-LIKE VACUOLE IN YEAST
酵母中溶酶体样液泡的蛋白质分类
  • 批准号:
    2176704
  • 财政年份:
    1983
  • 资助金额:
    $ 41.07万
  • 项目类别:

相似海外基金

Double Incorporation of Non-Canonical Amino Acids in an Animal and its Application for Precise and Independent Optical Control of Two Target Genes
动物体内非规范氨基酸的双重掺入及其在两个靶基因精确独立光学控制中的应用
  • 批准号:
    BB/Y006380/1
  • 财政年份:
    2024
  • 资助金额:
    $ 41.07万
  • 项目类别:
    Research Grant
Quantifying L-amino acids in Ryugu to constrain the source of L-amino acids in life on Earth
量化 Ryugu 中的 L-氨基酸以限制地球生命中 L-氨基酸的来源
  • 批准号:
    24K17112
  • 财政年份:
    2024
  • 资助金额:
    $ 41.07万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
Molecular recognition and enantioselective reaction of amino acids
氨基酸的分子识别和对映选择性反应
  • 批准号:
    23K04668
  • 财政年份:
    2023
  • 资助金额:
    $ 41.07万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Basic research toward therapeutic strategies for stress-induced chronic pain with non-natural amino acids
非天然氨基酸治疗应激性慢性疼痛策略的基础研究
  • 批准号:
    23K06918
  • 财政年份:
    2023
  • 资助金额:
    $ 41.07万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Molecular mechanisms how arrestins that modulate localization of glucose transporters are phosphorylated in response to amino acids
调节葡萄糖转运蛋白定位的抑制蛋白如何响应氨基酸而被磷酸化的分子机制
  • 批准号:
    23K05758
  • 财政年份:
    2023
  • 资助金额:
    $ 41.07万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Design and Synthesis of Fluorescent Amino Acids: Novel Tools for Biological Imaging
荧光氨基酸的设计与合成:生物成像的新工具
  • 批准号:
    2888395
  • 财政年份:
    2023
  • 资助金额:
    $ 41.07万
  • 项目类别:
    Studentship
Collaborative Research: RUI: Elucidating Design Rules for non-NRPS Incorporation of Amino Acids on Polyketide Scaffolds
合作研究:RUI:阐明聚酮化合物支架上非 NRPS 氨基酸掺入的设计规则
  • 批准号:
    2300890
  • 财政年份:
    2023
  • 资助金额:
    $ 41.07万
  • 项目类别:
    Continuing Grant
Structurally engineered N-acyl amino acids for the treatment of NASH
用于治疗 NASH 的结构工程 N-酰基氨基酸
  • 批准号:
    10761044
  • 财政年份:
    2023
  • 资助金额:
    $ 41.07万
  • 项目类别:
Lifestyle, branched-chain amino acids, and cardiovascular risk factors: a randomized trial
生活方式、支链氨基酸和心血管危险因素:一项随机试验
  • 批准号:
    10728925
  • 财政年份:
    2023
  • 资助金额:
    $ 41.07万
  • 项目类别:
Single-molecule protein sequencing by barcoding of N-terminal amino acids
通过 N 端氨基酸条形码进行单分子蛋白质测序
  • 批准号:
    10757309
  • 财政年份:
    2023
  • 资助金额:
    $ 41.07万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了