Evolution of the Cdk-activator Speedy/RINGO in vertebrates

Cell Mol Life Sci. 2012 Nov;69(22):3835-50. doi: 10.1007/s00018-012-1050-1. Epub 2012 Jul 5.


Successful completion of the cell cycle relies on the precise activation and inactivation of cyclin-dependent kinases (Cdks) whose activity is mainly regulated by binding to cyclins. Recently, a new family of Cdk regulators termed Speedy/RINGO has been discovered, which can bind and activate Cdks but shares no apparent amino acid sequence homology with cyclins. All Speedy proteins share a conserved domain of approximately 140 amino acids called "Speedy Box", which is essential for Cdk binding. Speedy/RINGO proteins display an important role in oocyte maturation in Xenopus. Interestingly, a common feature of all Speedy genes is their predominant expression in testis suggesting that meiotic functions may be the most important physiological feature of Speedy genes. Speedy homologs have been reported in mammals and can be traced back to the most primitive clade of chordates (Ciona intestinalis). Here, we investigated the evolution of the Speedy genes and have identified a number of new Speedy/RINGO proteins. Through extensive analysis of numerous species, we discovered diverse evolutionary histories: the number of Speedy genes varies considerably among species, with evidence of substantial gains and losses. Despite the interspecies variation, Speedy is conserved among most species examined. Our results provide a complete picture of the Speedy gene family and its evolution.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Biological Evolution
  • Cell Cycle / genetics
  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Chickens / genetics
  • Chickens / metabolism
  • Cyclin-Dependent Kinases / chemistry
  • Cyclin-Dependent Kinases / metabolism*
  • Evolution, Molecular*
  • Humans
  • Mice
  • Molecular Sequence Data
  • Pan troglodytes / genetics
  • Pan troglodytes / metabolism
  • Phylogeny
  • Protein Binding
  • Rats
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Sharks / genetics
  • Sharks / metabolism
  • Vertebrates / genetics
  • Vertebrates / metabolism
  • Xenopus Proteins / chemistry
  • Xenopus Proteins / genetics
  • Xenopus Proteins / metabolism
  • Xenopus laevis / genetics
  • Xenopus laevis / metabolism
  • Zebrafish / genetics
  • Zebrafish / metabolism


  • Cell Cycle Proteins
  • SPDYA protein, human
  • Xenopus Proteins
  • ls27 protein, Xenopus
  • Cyclin-Dependent Kinases