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E2f1-3 switch from activators in progenitor cells to repressors in differentiating cells
Jean-Leon Chong1, Pamela L Wenzel, M Teresa Sáenz-Robles
1Department of Molecular Virology, Immunology and Medical Genetics, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA.
Nature
|December 18, 2009
Summary
Retinoblastoma protein (Rb) and E2f activators (E2f1-3) have dual roles in cell cycle control. E2f1-3 are vital for progenitor cell survival, not division, and repress differentiation.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- The retinoblastoma protein (Rb) traditionally inhibits cell cycle progression by sequestering E2f activators (E2f1-3).
- E2f1-3 are considered key effectors driving cells into S phase and proliferation.
Purpose of the Study:
- To investigate the in vivo functions of E2f1, E2f2, and E2f3 in mammalian cell cycle control.
- To clarify the context-dependent roles of E2f1-3 as activators versus repressors.
Main Methods:
- Utilized tissue-specific cre-transgenic mice and conditional E2f alleles.
- Examined E2f1-3 triple deficiency in murine embryonic stem cells, embryos, and small intestines.
Main Results:
- In dividing progenitor cells, E2f1-3 act as activators but are dispensable for division, crucial for survival.
- In differentiating cells, E2f1-3 complex with Rb to repress E2f targets and promote cell cycle exit.
- Rb inactivation in differentiating cells switched E2f1-3 to activators, causing ectopic divisions; E2f1-3 loss rescued this.
Conclusions:
- E2f1-3 function dynamically as activators or repressors depending on cellular context (dividing vs. differentiating).
- E2f1-3 are essential for progenitor cell survival and play a critical role in cell cycle exit during differentiation.
- This study redefines the roles of E2f1-3 in normal and aberrant cell cycles, impacting cancer research.
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