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定量磷酸化蛋白质组学揭示了 ATR 激活剂 ETAA1 的有丝分裂功能。

Quantitative phosphoproteomics reveals mitotic function of the ATR activator ETAA1.

机构信息

Department of Biochemistry, Vanderbilt University School of Medicine, Vanderbilt University, Nashville, TN.

Department of Biochemistry, Vanderbilt University School of Medicine, Vanderbilt University, Nashville, TN

出版信息

J Cell Biol. 2019 Apr 1;218(4):1235-1249. doi: 10.1083/jcb.201810058. Epub 2019 Feb 12.

DOI:10.1083/jcb.201810058
PMID:30755469
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6446857/
Abstract

The ATR kinase controls cell cycle transitions and the DNA damage response. ATR activity is regulated through two ATR-activating proteins, ETAA1 and TOPBP1. To examine how each activator contributes to ATR signaling, we used quantitative mass spectrometry to identify changes in protein phosphorylation in ETAA1- or TOPBP1-deficient cells. We identified 724, 285, and 118 phosphosites to be regulated by TOPBP1, ETAA1, or both ATR activators, respectively. Gene ontology analysis of TOPBP1- and ETAA1-dependent phosphoproteins revealed TOPBP1 to be a primary ATR activator for replication stress, while ETAA1 regulates mitotic ATR signaling. Inactivation of ATR or ETAA1, but not TOPBP1, results in decreased Aurora B kinase activity during mitosis. Additionally, ATR activation by ETAA1 is required for proper chromosome alignment during metaphase and for a fully functional spindle assembly checkpoint response. Thus, we conclude that ETAA1 and TOPBP1 regulate distinct aspects of ATR signaling with ETAA1 having a dominant function in mitotic cells.

摘要

ATR 激酶控制细胞周期转变和 DNA 损伤反应。ATR 活性通过两种 ATR 激活蛋白 ETAA1 和 TOPBP1 进行调节。为了研究每个激活剂如何促进 ATR 信号传导，我们使用定量质谱法来鉴定 ETAA1 或 TOPBP1 缺陷细胞中蛋白质磷酸化的变化。我们分别鉴定出 724、285 和 118 个磷酸化位点受 TOPBP1、ETAA1 或两种 ATR 激活剂的调节。TOPBP1 和 ETAA1 依赖性磷酸化蛋白的基因本体分析表明，TOPBP1 是复制应激的主要 ATR 激活剂，而 ETAA1 调节有丝分裂 ATR 信号传导。ATR 或 ETAA1 的失活，但不是 TOPBP1 的失活，导致有丝分裂期间 Aurora B 激酶活性降低。此外，ETAA1 通过 ATR 的激活对于中期染色体正确排列以及完全功能性纺锤体组装检查点反应是必需的。因此，我们得出结论，ETAA1 和 TOPBP1 调节 ATR 信号传导的不同方面，ETAA1 在有丝分裂细胞中具有主要功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/569f/6446857/87dafdcb626c/JCB_201810058_Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/569f/6446857/e147c7dd8330/JCB_201810058_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/569f/6446857/af5277315b5c/JCB_201810058_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/569f/6446857/96f8e9f3c162/JCB_201810058_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/569f/6446857/bcefe29fcd0a/JCB_201810058_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/569f/6446857/360c27500b45/JCB_201810058_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/569f/6446857/6fd4f2b20ff7/JCB_201810058_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/569f/6446857/b19cc8be556a/JCB_201810058_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/569f/6446857/b117fcec2085/JCB_201810058_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/569f/6446857/87dafdcb626c/JCB_201810058_Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/569f/6446857/e147c7dd8330/JCB_201810058_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/569f/6446857/af5277315b5c/JCB_201810058_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/569f/6446857/96f8e9f3c162/JCB_201810058_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/569f/6446857/bcefe29fcd0a/JCB_201810058_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/569f/6446857/360c27500b45/JCB_201810058_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/569f/6446857/6fd4f2b20ff7/JCB_201810058_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/569f/6446857/b19cc8be556a/JCB_201810058_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/569f/6446857/b117fcec2085/JCB_201810058_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/569f/6446857/87dafdcb626c/JCB_201810058_Fig9.jpg

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[4]
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[7]
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[9]
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[2]
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[3]
The Effect of Replication Protein A Inhibition and Post-Translational Modification on ATR Kinase Signaling.

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[4]
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[5]
DBF4, not DRF1, is the crucial regulator of CDC7 kinase at replication forks.

J Cell Biol. 2024-8-5

[6]
Targeting ATR Pathway in Solid Tumors: Evidence of Improving Therapeutic Outcomes.

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[7]
Targeting ATR in Cancer Medicine.

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[8]
ATR promotes clearance of damaged DNA and damaged cells by rupturing micronuclei.

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[9]
The Adaptive Mechanisms and Checkpoint Responses to a Stressed DNA Replication Fork.

Int J Mol Sci. 2023-6-22

[10]
PTBP1 enforces ATR-CHK1 signaling determining the potency of CDC7 inhibitors.

iScience. 2023-5-26

本文引用的文献

[1]
An intrinsic S/G checkpoint enforced by ATR.

Science. 2018-8-24

[2]
Separable roles for Mec1/ATR in genome maintenance, DNA replication, and checkpoint signaling.

Genes Dev. 2018-6-13

[3]
A mitosis-specific and R loop-driven ATR pathway promotes faithful chromosome segregation.

Science. 2018-1-5

[4]
Plk1 bound to Bub1 contributes to spindle assembly checkpoint activity during mitosis.

Sci Rep. 2017-8-18

[5]
The essential kinase ATR: ensuring faithful duplication of a challenging genome.

Nat Rev Mol Cell Biol. 2017-10

[6]
RPA-Binding Protein ETAA1 Is an ATR Activator Involved in DNA Replication Stress Response.

Curr Biol. 2016-12-19

[7]
ETAA1 acts at stalled replication forks to maintain genome integrity.

Nat Cell Biol. 2016-11

[8]
Activation of the ATR kinase by the RPA-binding protein ETAA1.

Nat Cell Biol. 2016-10-10

[9]
Ewing Tumor-associated Antigen 1 Interacts with Replication Protein A to Promote Restart of Stalled Replication Forks.

J Biol Chem. 2016-10-14

[10]
Rapid Protein Depletion in Human Cells by Auxin-Inducible Degron Tagging with Short Homology Donors.

Cell Rep. 2016-3-24

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