The influence of reactive oxygen species on cell cycle progression in mammalian cells
Eline Hendrike Verbon1, Jan Andries Post, Johannes Boonstra
1University College Utrecht, P O Box 80145, 3508 TC Utrecht, The Netherlands.
Abstract:
Cell cycle regulation is performed by cyclins and cyclin dependent kinases (CDKs). Recently, it has become clear that reactive oxygen species (ROS) influence the presence and activity of these enzymes and thereby control cell cycle progression. In this review, we first describe the discovery of enzymes specialized in ROS production: the NADPH oxidase (NOX) complexes. This discovery led to the recognition of ROS as essential players in many cellular processes, including cell cycle progression. ROS influence cell cycle progression in a context-dependent manner via phosphorylation and ubiquitination of CDKs and cell cycle regulatory molecules. We show that ROS often regulate ubiquitination via intermediate phosphorylation and that phosphorylation is thus the major regulatory mechanism influenced by ROS. In addition, ROS have recently been shown to be able to activate growth factor receptors. We will illustrate the diverse roles of ROS as mediators in cell cycle regulation by incorporating phosphorylation, ubiquitination and receptor activation in a model of cell cycle regulation involving EGF-receptor activation. We conclude that ROS can no longer be ignored when studying cell cycle progression.
Insights
Reactive oxygen species (ROS) regulate cell cycle progression by influencing cyclin-dependent kinases (CDKs) through phosphorylation and ubiquitination. These findings highlight ROS as critical mediators in cell cycle control.
Area of Science:
- Cell Biology
- Biochemistry
Background:
- Cell cycle progression is tightly regulated by cyclins and cyclin-dependent kinases (CDKs).
- Reactive oxygen species (ROS) have emerged as crucial signaling molecules influencing cellular processes.
- The role of ROS in cell cycle regulation is increasingly recognized.
Purpose of the Study:
- To review the discovery and function of NADPH oxidase (NOX) complexes in ROS production.
- To elucidate the mechanisms by which ROS influence cell cycle progression.
- To integrate the roles of phosphorylation, ubiquitination, and receptor activation in ROS-mediated cell cycle control.
Main Methods:
- Review of existing literature on ROS, NOX complexes, and cell cycle regulation.
- Analysis of signaling pathways involving phosphorylation and ubiquitination.
- Development of a model illustrating ROS involvement in EGF-receptor-mediated cell cycle regulation.
Main Results:
- ROS, produced by NOX complexes, are essential regulators of cell cycle progression.
- ROS modulate CDK activity and cell cycle regulators via phosphorylation and ubiquitination.
- Phosphorylation is identified as the predominant regulatory mechanism influenced by ROS, often preceding ubiquitination.
- ROS can activate growth factor receptors, such as the EGF receptor, impacting cell cycle control.
Conclusions:
- ROS are significant mediators of cell cycle regulation, acting through diverse signaling pathways.
- Understanding ROS signaling is critical for comprehending cell cycle control.
- The interplay between ROS, phosphorylation, ubiquitination, and receptor activation provides a comprehensive view of cell cycle regulation.
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