Redox regulation of cell proliferation: Bioinformatics and redox proteomics approaches to identify redox-sensitive cell cycle regulators.

Redox regulation of cell proliferation: Bioinformatics and redox proteomics approaches to identify redox-sensitive cell cycle regulators.
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DOI:
10.1016/j.freeradbiomed.2018.03.047
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发表时间:
2018-07
影响因子:
7.4
通讯作者:
Wright MH
Wright MH
中科院分区:
医学1区
文献类型:
--
作者:
Foyer CH;Wilson MH;Wright MH

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植物干细胞是植物生长发育的基础。静止和分裂的平衡受到高度调节,同时确保增殖细胞免受可能损害基因组的环境波动的不利影响。氧化还原调节对于感知环境压力时增殖的激活和细胞周期的停滞都很重要。在这种情况下,活性氧作为“促生命”信号,在细胞周期和存活的调节中发挥积极作用。然而,人们对影响细胞周期进程的代谢机制和氧化还原敏感蛋白知之甚少。根据每种蛋白质的二级结构和溶剂可及性可能性,我们已经在拟南芥中已知的细胞周期调节因子上鉴定出半胱氨酸残基,这些残基是可能可接触的,并且可以在氧化还原调节中发挥作用。我们认为氧化还原调节可能与其他已知的翻译后修饰一起发挥作用,以控制核心细胞周期调节因子(例如视网膜母细胞瘤蛋白)的功能。由于我们目前对氧化还原调节如何参与细胞周期控制的理解因缺乏关于哪些残基重要以及这些残基的修饰如何改变蛋白质功能的知识而受到阻碍,因此我们讨论如何在分子水平上绘制关键的氧化还原修饰。核心细胞周期基因和复合物,显示可能可接近或暴露的半胱氨酸。彩色框显示可能暴露的半胱氨酸数量:橙色,0 暴露;绿色,1-3 个暴露;蓝色,4-12 暴露。活性氧作为“促生命”信号,在细胞周期的调节中发挥积极作用。细胞质和细胞核的氧化增加发生在细胞周期的早期阶段。半胱氨酸残基的翻译后修饰可能在细胞周期调节中发挥关键作用。我们已经鉴定了一组具有可接近或潜在暴露的半胱氨酸的细胞周期蛋白核心。表征氧化还原蛋白质组的新灵敏方法将鉴定氧化还原调节的细胞周期蛋白。
Plant stem cells are the foundation of plant growth and development. The balance of quiescence and division is highly regulated, while ensuring that proliferating cells are protected from the adverse effects of environment fluctuations that may damage the genome. Redox regulation is important in both the activation of proliferation and arrest of the cell cycle upon perception of environmental stress. Within this context, reactive oxygen species serve as ‘pro-life’ signals with positive roles in the regulation of the cell cycle and survival. However, very little is known about the metabolic mechanisms and redox-sensitive proteins that influence cell cycle progression. We have identified cysteine residues on known cell cycle regulators in Arabidopsis that are potentially accessible, and could play a role in redox regulation, based on secondary structure and solvent accessibility likelihoods for each protein. We propose that redox regulation may function alongside other known posttranslational modifications to control the functions of core cell cycle regulators such as the retinoblastoma protein. Since our current understanding of how redox regulation is involved in cell cycle control is hindered by a lack of knowledge regarding both which residues are important and how modification of those residues alters protein function, we discuss how critical redox modifications can be mapped at the molecular level. Core cell cycle genes and complexes, showing potentially accessible or exposed cysteines. Coloured boxes show the number of potentially exposed cysteines: Orange, 0 exposed; Green, 1–3 exposed; Blue, 4–12 exposed. Reactive oxygen species serve as ‘pro-life’ signals with positive roles in the regulation of the cell cycle. Increased oxidation of the cytosol and the nucleus occurs during the early stages of the cell cycle. Post translational modification of cysteine residues may play a key role in cell cycle regulation. We have identified a set of core of cell cycle proteins that have either accessible or potentially exposed cysteines. New sensitive methods to characterise the redox proteome will identify redox-regulated cell cycle proteins.
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