Meiotic inactivation of Xenopus Myt1 by CDK/XRINGO, but not CDK/cyclin, via site-specific phosphorylation

Mol Cell. 2008 Oct 24;32(2):210-20. doi: 10.1016/j.molcel.2008.08.029.


Cell-cycle progression is regulated by cyclin-dependent kinases (CDKs). CDK1 and CDK2 can be also activated by noncyclin proteins named RINGO/Speedy, which were identified as inducers of the G2/M transition in Xenopus oocytes. However, it is unclear how XRINGO triggers M phase entry in oocytes. We show here that XRINGO-activated CDKs can phosphorylate specific residues in the regulatory domain of Myt1, a Wee1 family kinase that plays a key role in the G2 arrest of oocytes. We have identified three Ser that are major phosphoacceptor sites for CDK/XRINGO but are poorly phosphorylated by CDK/cyclin. Phosphorylation of these Ser inhibits Myt1 activity, whereas their mutation makes Myt1 resistant to inhibition by CDK/XRINGO. Our results demonstrate that XRINGO-activated CDKs have different substrate specificity than the CDK/cyclin complexes. We also describe a mechanism of Myt1 regulation based on site-specific phosphorylation, which is likely to mediate the induction of G2/M transition in oocytes by XRINGO.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CDC2 Protein Kinase / metabolism
  • Cell Cycle Proteins / metabolism
  • Cell Cycle Proteins / physiology*
  • Cell Division / physiology
  • Cyclin B / physiology*
  • Cyclin-Dependent Kinase 2 / metabolism
  • Cyclin-Dependent Kinases / physiology*
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism*
  • Down-Regulation
  • Enzyme Activation
  • G2 Phase / physiology
  • Meiosis / physiology*
  • Oocytes / cytology
  • Oocytes / enzymology
  • Oocytes / metabolism
  • Phosphorylation
  • Substrate Specificity
  • Transcription Factors / chemistry
  • Transcription Factors / metabolism*
  • Xenopus
  • Xenopus Proteins / chemistry
  • Xenopus Proteins / metabolism*
  • Xenopus Proteins / physiology*


  • Cell Cycle Proteins
  • Cyclin B
  • DNA-Binding Proteins
  • Myt1 protein, Xenopus
  • Transcription Factors
  • Xenopus Proteins
  • ls27 protein, Xenopus
  • CDC2 Protein Kinase
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinases