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暴露于氧化应激下的整合磷酸化蛋白质组学和蛋白质组学分析

Integrative Phosphoproteomic and Proteomic Analysis of Exposed to Oxidative Stress.

作者信息

Arribas Víctor, Borrajo Ana, Hernáez María Luisa, Martínez Raquel, Monteoliva Lucía, Gil Concha, Molero Gloria

机构信息

Department of Microbiology and Parasitology, Faculty of Pharmacy, Complutense University of Madrid (UCM), 28040 Madrid, Spain.

Proteomics Unit, Biological Techniques Center, Complutense University of Madrid (UCM), 28040 Madrid, Spain.

出版信息

J Proteome Res. 2025 Jul 4;24(7):3484-3497. doi: 10.1021/acs.jproteome.5c00137. Epub 2025 Jun 2.

DOI:10.1021/acs.jproteome.5c00137
PMID:40454630
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12235712/
Abstract

is an opportunistic pathogen, which has recently been included in the high-priority list of pathogenic fungi by the World Health Organization (WHO). The scarce arsenal available to treat such invasive fungal infections makes the discovery of new antifungal targets an important task. This study utilizes DDA-MS technology to investigate both the phosphoproteomics and proteomics of during its late-stage response to oxidative stress induced by HO, aiming to identify key proteins involved. Phosphorylation, as an important post-translational modification, plays a crucial role in the ability of to survive oxidative stress. Our study enabled the identification and quantification of important changes in both protein abundance and phosphorylation events across multiple proteins following a 200 min 10 mM HO treatment. The use of the DDA-MS approach allowed for the identification of new actors in the response to oxidative stress. Novel phosphorylation sites were identified in kinases and transcription factors. Regarding protein kinases, Cdc5-reduced phosphorylation may mediate a transient G2 cell cycle arrest, while Kis1─the regulatory β-subunit of Snf1 kinase─might play a role in ROS scavenging following oxidative stress. In terms of transcription factors, Gzf3-decreased phosphorylation was essential for cell survival and ROS detoxification after oxidative stress.

摘要

是一种机会致病菌,最近被世界卫生组织(WHO)列入高优先级致病真菌名单。治疗此类侵袭性真菌感染的可用手段匮乏,这使得发现新的抗真菌靶点成为一项重要任务。本研究利用数据依赖型采集质谱(DDA-MS)技术,研究其在对过氧化氢(HO)诱导的氧化应激的晚期反应过程中的磷酸蛋白质组学和蛋白质组学,旨在鉴定其中涉及的关键蛋白质。磷酸化作为一种重要的翻译后修饰,在其应对氧化应激的能力中起着关键作用。我们的研究能够鉴定和量化在200分钟10毫摩尔HO处理后多种蛋白质的丰度和磷酸化事件中的重要变化。使用DDA-MS方法能够鉴定氧化应激反应中的新参与者。在激酶和转录因子中鉴定出了新的磷酸化位点。关于蛋白激酶,Cdc5磷酸化水平降低可能介导短暂的G2期细胞周期阻滞,而Kis1(Snf1激酶的调节β亚基)可能在氧化应激后的活性氧清除中发挥作用。就转录因子而言,Gzf3磷酸化水平降低对于氧化应激后的细胞存活和活性氧解毒至关重要。

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本文引用的文献

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Antioxidants (Basel). 2024 Apr 26;13(5):527. doi: 10.3390/antiox13050527.
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Regulation of copper uptake by the SWI/SNF chromatin remodeling complex in Candida albicans affects susceptibility to antifungal and oxidative stresses under hypoxia.调控铜摄取的 SWI/SNF 染色质重塑复合物在白色念珠菌中影响缺氧条件下对抗真菌和氧化应激的敏感性。
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Novel Roles of the Greatwall Kinase Rim15 in Yeast Oxidative Stress Tolerance through Mediating Antioxidant Systems and Transcriptional Regulation.
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Antioxidants (Basel). 2024 Feb 21;13(3):260. doi: 10.3390/antiox13030260.
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Global incidence and mortality of severe fungal disease.全球严重真菌感染的发病率和死亡率。
Lancet Infect Dis. 2024 Jul;24(7):e428-e438. doi: 10.1016/S1473-3099(23)00692-8. Epub 2024 Jan 12.
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Fenton-like Chemistry by a Copper(I) Complex and HO Relevant to Enzyme Peroxygenase C-H Hydroxylation.铜(I)配合物与 HO 引发的芬顿样化学与酶过氧化物酶 C-H 羟化的关系。
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Stress- and metabolic responses of Candida albicans require Tor1 kinase N-terminal HEAT repeats.白色念珠菌的应激和代谢反应需要 Tor1 激酶 N 端 HEAT 重复序列。
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