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Updated: Aug 14, 2026
12:19
Analysis of Cell Cycle Position in Mammalian Cells
Published on: January 21, 2012
Bcl2 retards G1/S cell cycle transition by regulating intracellular ROS
Xingming Deng1, Fengqin Gao, W Stratford May
1University of Florida Shands Cancer Center, 1600 SW Archer Rd, Medical Science Building, Gainesville, FL 32610-0232, USA.
Blood
|July 12, 2003
Summary
Bcl2 phosphorylation regulates cell cycle progression by controlling reactive oxygen species (ROS) levels. This discovery reveals a novel signaling pathway linking Bcl2
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Bcl2's anti-apoptotic role is phosphorylation-dependent.
- Bcl2's influence on cell cycle progression lacks a clear molecular mechanism.
- Bcl2 functions in mitochondria as an antioxidant, potentially regulating reactive oxygen species (ROS).
Purpose of the Study:
- To investigate if Bcl2 phosphorylation regulates ROS and cell cycle progression.
- To elucidate the molecular mechanism linking Bcl2, ROS, and cell cycle control.
Main Methods:
- Utilized gain-of-function phosphomimetic (S70E, EEE) and non-phosphorylatable (S70A, AAA) Bcl2 mutants.
- Measured G1 --> S transition and intracellular ROS levels in transfected cells.
- Assessed effects of interleukin-3 withdrawal and antioxidant treatment (PDTC).
Main Results:
- Phosphomimetic Bcl2 mutants (S70E, EEE) significantly retarded G1 --> S transition and cell growth.
- These mutants were associated with reduced intracellular ROS levels.
- Reduced ROS, via Bcl2 mutants, IL-3 withdrawal, or PDTC, led to p27 upregulation and G0/G1 cell cycle arrest.
- H2O2 addition overrode G1 --> S retardation, involving p27 downregulation and Cdk2 activation.
Conclusions:
- Bcl2 phosphorylation regulates G1 --> S transition via a novel mechanism involving ROS, p27, and Cdk2.
- Phosphorylation functionally links Bcl2's anti-apoptotic, cell cycle retardation, and antioxidant functions.
- Bcl2's role in cell cycle control is mediated through modulation of intracellular ROS levels.
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