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Published on: June 6, 2017
The NADPH oxidases NOX4 and DUOX2 regulate cell cycle entry via a p53-dependent pathway
1Department of Chemical and Systems Biology, Stanford University School of Medicine Clark Center W200, Stanford, CA, USA. asalmeen@lbl.gov
Oncogene
|June 10, 2010
Summary
Reactive oxygen species (ROS), generated by NOX4 and DUOX2, are crucial for cell cycle entry. These proteins regulate proliferation via a p53-dependent checkpoint, not early growth factor signaling.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Reactive oxygen species (ROS) play a role in cell proliferation signaling pathways.
- Mechanisms of ROS generation and their specific molecular targets in cell growth are not fully understood.
Purpose of the Study:
- To identify redox-related proteins essential for growth factor-induced cell cycle entry.
- To elucidate the role of NADPH oxidases NOX4 and DUOX2 in platelet-derived growth factor (PDGF) signaling.
Main Methods:
- Utilized a focused siRNA screen to identify key redox-related proteins.
- Investigated the impact of NOX4 and DUOX2 knockdown on signaling pathways, protein phosphorylation, and cell cycle regulators.
Main Results:
- NOX4 and DUOX2 are required for PDGF-induced retinoblastoma protein (Rb) phosphorylation.
- Knockdown of NOX4/DUOX2 did not affect early cyclin D1 upregulation but reduced ERK1 phosphorylation hours post-stimulation.
- NOX4/DUOX2 knockdown increased levels of p53 and p21 (Waf1/Cip1), indicating activation of a p53-dependent pathway.
Conclusions:
- NOX4 and DUOX2 regulate cell cycle entry through a p53-dependent checkpoint mechanism.
- Their function in proliferation appears to be independent of direct effects on early growth factor receptor signaling.
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