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The Ets transcription factor GABP is required for cell-cycle progression
Zhong-Fa Yang1, Stephanie Mott, Alan G Rosmarin
1Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI 02912, USA.
Nature Cell Biology
|February 6, 2007
Summary
The Ets transcription factor GABP is essential for cell cycle re-entry from quiescence. GABP drives DNA synthesis and CDKI degradation via a novel pathway, distinct from D-type cyclins and CDKs.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- Cellular quiescence (G0) to S phase transition is typically regulated by D-type cyclins, cyclin-dependent kinases (Cdks), Cdk inhibitors (CDKIs), and Rb-E2F interactions.
- Fibroblasts lacking D-type cyclins can still proliferate, suggesting alternative pathways for cell cycle entry exist.
Purpose of the Study:
- To investigate the role of the Ets transcription factor Gabpalpha (GABP) in serum-induced cell cycle re-entry.
- To elucidate the molecular mechanisms by which GABP regulates proliferation.
Main Methods:
- Ectopic expression of Gabpalpha in quiescent cells.
- Genetic disruption of Gabpalpha.
- Analysis of gene expression related to cell cycle progression, DNA synthesis, and CDKI degradation.
- Assessment of Rb-E2F activity.
Main Results:
- Serum induces Gabpalpha expression, and its ectopic expression promotes cell cycle re-entry.
- Gabpalpha disruption prevents S phase entry and reduces expression of DNA synthesis genes and CDKI degradation.
- Gabpalpha acts independently of D-type cyclins, Cdks, Rb, and E2Fs.
Conclusions:
- GABP is both necessary and sufficient for quiescent cells to re-enter the cell cycle.
- GABP regulates a novel pathway for cell cycle re-entry, distinct from the canonical D-type cyclin/Cdk pathway.
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