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12:19
Analysis of Cell Cycle Position in Mammalian Cells
Published on: January 21, 2012
The E2F1-3 transcription factors are essential for cellular proliferation
1Division of Human Cancer Genetics, Department of Molecular Virology, Immunology and Medical Genetics, and Department of Molecular Genetics, The Ohio State University, Columbus, Ohio 43210, USA.
Nature
|November 24, 2001
Summary
The combined loss of E2F1, E2F2, and E2F3 transcription factors halts cell cycle progression and proliferation. This study provides genetic evidence for the essential role of these E2F factors in cell development.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- The retinoblastoma (Rb) tumor suppressor pathway controls cellular proliferation by regulating E2F transcription factors.
- E2F1, E2F2, and E2F3 are a subclass of E2F factors crucial for G1/S phase transition.
Purpose of the Study:
- To investigate the role of E2F1, E2F2, and E2F3 in cell cycle progression and proliferation.
- To elucidate the function of this E2F subclass in the Rb pathway.
Main Methods:
- Conditional gene targeting in mouse embryonic fibroblasts.
- Analysis of E2F target gene expression.
- Assessment of cell cycle progression, mitosis, and proliferation.
Main Results:
- Combined loss of E2F1, E2F2, and E2F3 severely impaired E2F target gene expression.
- Loss of these E2F factors abolished S phase entry, mitosis, and proliferation.
- E2F loss elevated p21Cip1, decreased cyclin-dependent kinase activity, and reduced Rb phosphorylation.
Conclusions:
- This E2F subclass acts in a positive feedback loop by down-modulating p21Cip1.
- This mechanism inactivates Rb-dependent repression, enabling S phase entry.
- Direct genetic evidence confirms the essential role of E2F1, E2F2, and E2F3 in cell cycle control, proliferation, and development.
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