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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
PubMed

Insights

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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