• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

pADP-ribosylation 调节 HuR 的细胞质定位、切割和促凋亡功能。

pADP-ribosylation regulates the cytoplasmic localization, cleavage, and pro-apoptotic function of HuR.

机构信息

Department of Biochemistry, McGill University, Montreal, Canada.

Rosalind & Morris Goodman Cancer Institute, McGill University, Montreal, Canada.

出版信息

Life Sci Alliance. 2024 Mar 27;7(6). doi: 10.26508/lsa.202302316. Print 2024 Jun.

DOI:10.26508/lsa.202302316
PMID:38538092
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10972696/
Abstract

HuR (ElavL1) is one of the main post-transcriptional regulators that determines cell fate. Although the role of HuR in apoptosis is well established, the post-translational modifications that govern this function remain elusive. In this study, we show that PARP1/2-mediated poly(ADP)-ribosylation (PARylation) is instrumental in the pro-apoptotic function of HuR. During apoptosis, a substantial reduction in HuR PARylation is observed. This results in the cytoplasmic accumulation and the cleavage of HuR, both of which are essential events for apoptosis. These effects are mediated by a pADP-ribose-binding motif within the HuR-HNS region (HuR PAR-binding site). Under normal conditions, the association of the HuR PAR-binding site with pADP-ribose is responsible for the nuclear retention of HuR. Mutations within this motif prevent the binding of HuR to its import factor TRN2, leading to its cytoplasmic accumulation and cleavage. Collectively, our findings underscore the role of PARylation in controlling the pro-apoptotic function of HuR, offering insight into the mechanism by which PARP1/2 enzymes regulate cell fate and adaptation to various assaults.

摘要

HuR（ElavL1）是决定细胞命运的主要转录后调节因子之一。尽管 HuR 在细胞凋亡中的作用已得到充分证实，但调节此功能的翻译后修饰仍不清楚。在这项研究中，我们表明 PARP1/2 介导的聚（ADP-核糖）化（PARylation）对 HuR 的促凋亡功能至关重要。在细胞凋亡过程中，HuR 的 PARylation 大量减少。这导致 HuR 的细胞质积累和切割，这两者都是凋亡所必需的事件。这些效应是通过 HuR-HNS 区域（HuR PAR 结合位点）内的一个 pADP-核糖结合基序介导的。在正常情况下，HuR PAR 结合位点与 pADP-核糖的结合负责 HuR 的核保留。该基序内的突变阻止 HuR 与其输入因子 TRN2 的结合，导致其细胞质积累和切割。总之，我们的研究结果强调了 PARylation 在控制 HuR 的促凋亡功能中的作用，为 PARP1/2 酶如何调节细胞命运和适应各种攻击提供了深入了解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b91/10972696/42c91e2e7435/LSA-2023-02316_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b91/10972696/89df0e46057f/LSA-2023-02316_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b91/10972696/d959698615e4/LSA-2023-02316_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b91/10972696/dc70f8da6edc/LSA-2023-02316_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b91/10972696/c9ac10276075/LSA-2023-02316_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b91/10972696/b2ff931c5bda/LSA-2023-02316_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b91/10972696/d937db57ba85/LSA-2023-02316_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b91/10972696/70f4dd2e7e81/LSA-2023-02316_FigS4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b91/10972696/e90e0e7cc71a/LSA-2023-02316_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b91/10972696/87d1eba089b4/LSA-2023-02316_FigS5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b91/10972696/3e5f6005ee41/LSA-2023-02316_FigS6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b91/10972696/3d78693666b2/LSA-2023-02316_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b91/10972696/42c91e2e7435/LSA-2023-02316_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b91/10972696/89df0e46057f/LSA-2023-02316_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b91/10972696/d959698615e4/LSA-2023-02316_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b91/10972696/dc70f8da6edc/LSA-2023-02316_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b91/10972696/c9ac10276075/LSA-2023-02316_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b91/10972696/b2ff931c5bda/LSA-2023-02316_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b91/10972696/d937db57ba85/LSA-2023-02316_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b91/10972696/70f4dd2e7e81/LSA-2023-02316_FigS4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b91/10972696/e90e0e7cc71a/LSA-2023-02316_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b91/10972696/87d1eba089b4/LSA-2023-02316_FigS5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b91/10972696/3e5f6005ee41/LSA-2023-02316_FigS6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b91/10972696/3d78693666b2/LSA-2023-02316_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b91/10972696/42c91e2e7435/LSA-2023-02316_Fig6.jpg

相似文献

1
pADP-ribosylation regulates the cytoplasmic localization, cleavage, and pro-apoptotic function of HuR.pADP-ribosylation 调节 HuR 的细胞质定位、切割和促凋亡功能。
Life Sci Alliance. 2024 Mar 27;7(6). doi: 10.26508/lsa.202302316. Print 2024 Jun.
2
Poly (ADP-ribose) polymerase 1 promotes HuR/ELAVL1 cytoplasmic localization and inflammatory gene expression by regulating p38 MAPK activity.多聚（ADP-核糖）聚合酶 1 通过调节 p38 MAPK 活性促进 HuR/ELAVL1 细胞质定位和炎性基因表达。
Cell Mol Life Sci. 2024 Jun 9;81(1):253. doi: 10.1007/s00018-024-05292-2.
3
PARP1 promotes gene expression at the post-transcriptiona level by modulating the RNA-binding protein HuR.PARP1 通过调节 RNA 结合蛋白 HuR 促进转录后水平的基因表达。
Nat Commun. 2017 Mar 8;8:14632. doi: 10.1038/ncomms14632.
4
Poly(ADP-ribosyl)ation enhances HuR oligomerization and contributes to pro-inflammatory gene mRNA stabilization.多聚（ADP-核糖）化增强 HuR 寡聚化，并有助于促炎基因 mRNA 的稳定。
Cell Mol Life Sci. 2021 Feb;78(4):1817-1835. doi: 10.1007/s00018-020-03618-4. Epub 2020 Aug 13.
5
HPF1 regulates tendon stem/progenitor cell senescence and tendon repair via PARP1-mediated poly-ADP ribosylation of HuR.HPF1 通过 PARP1 介导的 HuR 多聚 ADP 核糖基化调控肌腱干/祖细胞衰老和肌腱修复。
Genes Genomics. 2024 Jan;46(1):27-36. doi: 10.1007/s13258-023-01447-w. Epub 2023 Sep 15.
6
Transportin 2 regulates apoptosis through the RNA-binding protein HuR.转运蛋白 2 通过 RNA 结合蛋白 HuR 调节细胞凋亡。
J Biol Chem. 2011 Jul 22;286(29):25983-91. doi: 10.1074/jbc.M110.216184. Epub 2011 Jun 6.
7
Cell-Penetrating Peptide TAT-HuR-HNS3 Suppresses Proinflammatory Gene Expression via Competitively Blocking Interaction of HuR with Its Partners.穿膜肽 TAT-HuR-HNS3 通过竞争性阻断 HuR 与其结合伙伴的相互作用来抑制促炎基因表达。
J Immunol. 2022 May 15;208(10):2376-2389. doi: 10.4049/jimmunol.2200002. Epub 2022 Apr 20.
8
The Enigmatic Function of PARP1: From PARylation Activity to PAR Readers.PARP1 的神秘功能：从 PAR 化酶活性到 PAR 阅读蛋白。
Cells. 2019 Dec 12;8(12):1625. doi: 10.3390/cells8121625.
9
Regulatory apoptotic fragment of PARP1 complements catalytic fragment for PAR and DNA-dependent activity but inhibits DNA-induced catalytic stimulation of PARP2.PARP1 的调控性凋亡片段补充了 PAR 和 DNA 依赖性活性的催化片段，但抑制了 PARP2 的 DNA 诱导的催化刺激。
DNA Repair (Amst). 2024 Jan;133:103593. doi: 10.1016/j.dnarep.2023.103593. Epub 2023 Nov 15.
10
Role of YB-1 in Regulation of Poly(ADP-Ribosylation) Catalyzed by Poly(ADP-Ribose) Polymerases.YB-1 在多聚（ADP-核糖）聚合酶催化的多聚（ADP-核糖）化调节中的作用。
Biochemistry (Mosc). 2022 Jan;87(Suppl 1):S32-S0. doi: 10.1134/S0006297922140048.

引用本文的文献

1
An HuR mutant, HuR-V225I, identified in adult T-cell Leukemia/Lymphoma, alters the pro-apoptotic function of HuR.在成人T细胞白血病/淋巴瘤中鉴定出的一种HuR突变体HuR-V225I，改变了HuR的促凋亡功能。
Cell Death Discov. 2024 Dec 18;10(1):503. doi: 10.1038/s41420-024-02268-w.

本文引用的文献

1
Beyond PARP1: The Potential of Other Members of the Poly (ADP-Ribose) Polymerase Family in DNA Repair and Cancer Therapeutics.超越PARP1：聚（ADP - 核糖）聚合酶家族其他成员在DNA修复和癌症治疗中的潜力
Front Cell Dev Biol. 2022 Jan 14;9:801200. doi: 10.3389/fcell.2021.801200. eCollection 2021.
2
Why structure and chain length matter: on the biological significance underlying the structural heterogeneity of poly(ADP-ribose).为什么结构和链长很重要：探讨多聚（ADP-核糖）结构异质性的生物学意义。
Nucleic Acids Res. 2021 Sep 7;49(15):8432-8448. doi: 10.1093/nar/gkab618.
3
Immunoprecipitation of Ribosome-Bound mRNAs from Astrocytic Perisynaptic Processes of the Mouse Hippocampus.
免疫沉淀法从鼠海马体星形细胞突触旁过程中提取核糖体结合的 mRNAs。
STAR Protoc. 2020 Dec 4;1(3):100198. doi: 10.1016/j.xpro.2020.100198. eCollection 2020 Dec 18.
4
The 89-kDa PARP1 cleavage fragment serves as a cytoplasmic PAR carrier to induce AIF-mediated apoptosis.89kDa 的 PARP1 切割片段作为细胞质 PAR 载体诱导 AIF 介导线粒体凋亡。
J Biol Chem. 2021 Jan-Jun;296:100046. doi: 10.1074/jbc.RA120.014479. Epub 2020 Nov 24.
5
Poly(ADP-ribosyl)ation enhances HuR oligomerization and contributes to pro-inflammatory gene mRNA stabilization.多聚（ADP-核糖）化增强 HuR 寡聚化，并有助于促炎基因 mRNA 的稳定。
Cell Mol Life Sci. 2021 Feb;78(4):1817-1835. doi: 10.1007/s00018-020-03618-4. Epub 2020 Aug 13.
6
PARPs and ADP-ribosylation in RNA biology: from RNA expression and processing to protein translation and proteostasis.PARPs 和 RNA 生物学中的 ADP-ribosylation：从 RNA 表达和加工到蛋白质翻译和蛋白质稳态。
Genes Dev. 2020 Mar 1;34(5-6):302-320. doi: 10.1101/gad.334433.119. Epub 2020 Feb 6.
7
The Enigmatic Function of PARP1: From PARylation Activity to PAR Readers.PARP1 的神秘功能：从 PAR 化酶活性到 PAR 阅读蛋白。
Cells. 2019 Dec 12;8(12):1625. doi: 10.3390/cells8121625.
8
Novel insights into PARPs in gene expression: regulation of RNA metabolism.PARPs 在基因表达中的新见解：RNA 代谢的调控。
Cell Mol Life Sci. 2019 Sep;76(17):3283-3299. doi: 10.1007/s00018-019-03120-6. Epub 2019 May 4.
9
Poly(ADP-ribosyl)ation by PARP1: reaction mechanism and regulatory proteins.聚（ADP-核糖）化由 PARP1 介导：反应机制和调节蛋白。
Nucleic Acids Res. 2019 May 7;47(8):3811-3827. doi: 10.1093/nar/gkz120.
10
PARylation regulates stress granule dynamics, phase separation, and neurotoxicity of disease-related RNA-binding proteins.聚泛素化调节应激颗粒的动态变化、疾病相关 RNA 结合蛋白的液-液相分离和神经毒性。
Cell Res. 2019 Mar;29(3):233-247. doi: 10.1038/s41422-019-0141-z. Epub 2019 Feb 6.