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E2f3 is critical for normal cellular proliferation
P O Humbert1, R Verona, J M Trimarchi
1Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 USA.
Genes & Development
|March 25, 2000
Summary
The transcription factor E2F3 is crucial for normal development and cellular proliferation. E2F3 deficiency impairs gene activation, impacting cell cycle progression and tumor cell growth.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- E2F transcription factors regulate cell proliferation and differentiation.
- The specific role of E2F3 in vivo was not fully understood.
Purpose of the Study:
- To investigate the in vivo function of E2F3.
- To determine the molecular mechanisms underlying E2F3's role in cell cycle regulation.
Main Methods:
- Generation of an E2f3 mutant mouse strain.
- Analysis of embryonic fibroblasts from E2f3-deficient mice.
- Assessment of gene expression and cell cycle progression.
Main Results:
- E2F3-deficient mice showed developmental defects.
- E2F3 deficiency impaired mitogen-induced transcription of E2F-responsive genes.
- E2F3 regulates key cell cycle genes (e.g., B-myb, cyclin A, cdc2, cdc6, DHFR) and controls proliferation rates.
Conclusions:
- E2F3 is essential for normal development and cellular proliferation.
- E2F3 acts as a critical regulator of the G(1)/S transition and DNA synthesis.
- E2F3 is rate-limiting for the proliferation of tumor cell lines.