DNA修复成分EEPD1调控肌动蛋白聚合

IF 2.4 4区 生物学 Q4 CELL BIOLOGY
Robert Hromas, Austin Kirby, Andrew Carrillo, Aruna Jasiwal, Kimi Kong, Manh Tien Tran, Dominic Arris, Elizabeth A. Williamson
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引用次数: 0

摘要

内切酶外切酶磷酸酶结构域蛋白1 (EEPD1)是具有DNA内切酶活性的DNase1超家族成员。它在氧化损伤修复和应激复制叉修复等多种DNA修复过程中起着关键作用。有趣的是,当胆固醇水平升高时,EEPD1在其氨基端附近发生肉豆蔻酰基化和棕榈酰化,这使得EEPD1蛋白定位于细胞膜内。令人惊讶的是,我们发现EEPD1促进皮层分支肌动蛋白聚合和适当的板足形成,并且是随后的细胞迁移所必需的。EEPD1增强肌动蛋白聚合部分需要其肉豆蔻酰化和棕榈酰化。EEPD1缺失也导致细胞核形态明显异常。EEPD1的缺失导致SRC、RAC1、contactn和profilin磷酸化缺失,这些磷酸化是肌动蛋白聚合信号传导的重要步骤。EEPD1缺失会降低SRC激酶活性,从而损害肌动蛋白聚合。综上所述,EEPD1是肌动蛋白聚合信号通路的一种新型正调控因子,将肌动蛋白调控与核形态和DNA修复联系起来。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

The DNA Repair Component EEPD1 Regulates Actin Polymerization

The DNA Repair Component EEPD1 Regulates Actin Polymerization

Endonuclease exonuclease phosphatase domain-containing protein 1 (EEPD1) is a DNase1 superfamily member that has DNA endonuclease activity. It plays a critical role in multiple DNA repair processes such as oxidative damage repair and stressed replication fork repair. Interestingly, EEPD1 is myristoylated and palmitoylated near its amino terminus in response to high levels of cholesterol, and this localizes EEPD1 protein to the inner cell membrane. Surprisingly, we found that EEPD1 promotes cortical branching actin polymerization and proper lamellipodia formation and is necessary for subsequent cell migration. EEPD1's enhancement of actin polymerization partially required its myristoylation and palmitoylation. EEPD1 depletion also resulted in marked abnormalities in nuclear morphology. Loss of EEPD1 resulted in loss of phosphorylation of SRC, RAC1, cortactin, and profilin, which are essential steps in signaling for actin polymerization. Loss of EEPD1 lowered SRC kinase activity, which would harm actin polymerization. In summary, EEPD1 is a novel, positive regulator of the signaling pathway for actin polymerization, linking actin regulation to nuclear morphology and DNA repair.

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来源期刊
Biology of the Cell
Biology of the Cell 生物-细胞生物学
CiteScore
5.30
自引率
0.00%
发文量
53
审稿时长
>12 weeks
期刊介绍: The journal publishes original research articles and reviews on all aspects of cellular, molecular and structural biology, developmental biology, cell physiology and evolution. It will publish articles or reviews contributing to the understanding of the elementary biochemical and biophysical principles of live matter organization from the molecular, cellular and tissues scales and organisms. This includes contributions directed towards understanding biochemical and biophysical mechanisms, structure-function relationships with respect to basic cell and tissue functions, development, development/evolution relationship, morphogenesis, stem cell biology, cell biology of disease, plant cell biology, as well as contributions directed toward understanding integrated processes at the organelles, cell and tissue levels. Contributions using approaches such as high resolution imaging, live imaging, quantitative cell biology and integrated biology; as well as those using innovative genetic and epigenetic technologies, ex-vivo tissue engineering, cellular, tissue and integrated functional analysis, and quantitative biology and modeling to demonstrate original biological principles are encouraged.
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