Negative regulation of cell-cycle progression by RINGO/Speedy E.
Cell-cycle transitions are controlled by CDKs (cyclin-dependent kinases), 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 with cyclins. The RINGO/Speedy family members studied so far positively regulate cell-cycle progression. In the present paper, 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.
Dinarina
Ana
A
CNIO (Spanish National Cancer Center), Melchor Fernández Almagro 3, 28029 Madrid, Spain.
Ruiz
E Josué
EJ
O'Loghlen
Ana
A
Mouron
Silvana
S
Perez
Laurent
L
Nebreda
Angel R
AR
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D049109:Cell Proliferation; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D013379:Substrate Specificity; D014981:Xenopus; D029867:Xenopus Proteins / Q000378:metabolism / Q000502:physiology*
D018797:Cell Cycle Proteins; D029867:Xenopus Proteins; C119055:ls27 protein, Xenopus; D018844:Cyclin-Dependent Kinases