A ROS-dependent mechanism promotes CDK2 phosphorylation to drive progression through S phase.
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Date
2022-07-25Author
Kirova, DG
Judasova, K
Vorhauser, J
Zerjatke, T
Leung, JK
Glauche, I
Mansfeld, J
Type
Journal Article
Metadata
Show full item recordAbstract
Reactive oxygen species (ROS) at the right concentration promote cell proliferation in cell culture, stem cells, and model organisms. However, the mystery of how ROS signaling is coordinated with cell cycle progression and integrated into the cell cycle control machinery on the molecular level remains unsolved. Here, we report increasing levels of mitochondrial ROS during the cell cycle in human cell lines that target cyclin-dependent kinase 2 (CDK2). Chemical and metabolic interferences with ROS production decrease T-loop phosphorylation on CDK2 and so impede its full activation and thus its efficient DNA replication. ROS regulate CDK2 activity through the oxidation of a conserved cysteine residue near the T-loop, which prevents the binding of the T-loop phosphatase KAP. Together, our data reveal how mitochondrial metabolism is coupled with DNA replication and cell cycle progression via ROS, thereby demonstrating how KAP activity toward CDKs can be cell cycle regulated.
Collections
Research team
Post-transl modification
Language
eng
Date accepted
2022-07-01
License start date
2022-07-01
Citation
Developmental Cell, 2022,
Publisher
CELL PRESS