Negative regulation of cell cycle progression by RINGO/Speedy E
Résumé
Cell cycle transitions are controlled by cyclin-dependent kinases (CDKs), whose activation is usually associated with the binding of cyclins. RINGO/Speedy proteins can also bind to and activate CDKs, although they do not have amino acid sequence homology to cyclins. The RINGO/Speedy family members studied so far positively regulate cell cycle progression. Here we report the biochemical and functional characterization of RINGO/Speedy E. We show that RINGO/Speedy E is a functionally distant member of this protein family that negatively affects cell cycle progression. RINGO/Speedy E overexpression inhibits the meiotic progression in Xenopus oocytes as well as the proliferation of mammalian cells. RINGO/Speedy E can bind to endogenous CDK1 and CDK2 in both cellular systems. However, the RINGO/Speedy E-activated CDKs have different substrate specificity than the CDKs activated by other RINGO/Speedy proteins, which may account for their different effects on the cell cycle. Our results indicate that although all RINGO/Speedy family members can activate CDKs, they may differently regulate cell cycle progression.
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