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

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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.Graphical abstractCore 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.HighlightsReactive 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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