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Negative regulation of cell-cycle progression by RINGO/Speedy E
Ana Dinarina1, E Josué Ruiz, Ana O'Loghlen
1CNIO (Spanish National Cancer Center), Melchor Fernández Almagro 3, 28029 Madrid, Spain.
The Biochemical Journal
|December 13, 2007
Summary
RINGO/Speedy E negatively regulates cell-cycle progression by binding cyclin-dependent kinases (CDKs). Unlike other RINGO/Speedy proteins, it inhibits meiotic and cell proliferation, indicating diverse roles in cell cycle control.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Cell-cycle transitions are regulated by cyclin-dependent kinases (CDKs).
- RINGO/Speedy proteins activate CDKs but lack homology to cyclins.
- Existing RINGO/Speedy family members promote cell-cycle progression.
Purpose of the Study:
- To biochemically and functionally characterize RINGO/Speedy E.
- To determine the role of RINGO/Speedy E in cell-cycle regulation.
- To investigate the interaction of RINGO/Speedy E with CDKs.
Main Methods:
- Overexpression of RINGO/Speedy E in Xenopus oocytes and mammalian cells.
- Biochemical assays to assess CDK binding and activity.
- Analysis of substrate specificity of CDK complexes.
Main Results:
- RINGO/Speedy E negatively impacts cell-cycle progression.
- Overexpression inhibits meiotic progression in Xenopus oocytes and proliferation in mammalian cells.
- RINGO/Speedy E binds CDK1 and CDK2, but activates them with altered substrate specificity compared to other RINGO/Speedy proteins.
Conclusions:
- RINGO/Speedy E is a functionally distinct member of the RINGO/Speedy family.
- RINGO/Speedy E's unique CDK activation leads to cell-cycle inhibition.
- Different RINGO/Speedy proteins exhibit diverse regulatory effects on the cell cycle.
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