Emi2 at the crossroads: where CSF meets MPF

Cell Cycle. 2007 Mar 15;6(6):732-8. doi: 10.4161/cc.6.6.3937. Epub 2007 Mar 14.

Abstract

Vertebrate eggs arrest at metaphase of meiosis II due to an activity known as cytostatic factor (CSF). CSF antagonizes the ubiquitin ligase activity of the anaphase-promoting complex/cyclosome (APC/C), preventing cyclin B destruction and meiotic exit until fertilization occurs. A puzzling feature of CSF arrest is that APC/C inhibition is leaky. Ongoing cyclin B synthesis is counterbalanced by a limited amount of APC/C-mediated cyclin B destruction; thus, cyclin B/Cdc2 activity remains at steady state. How the APC/C can be slightly active toward cyclin B, and yet restrained from ubiquitinating cyclin B altogether, is unknown. Emi2/XErp1 is the critical CSF component directly responsible for APC/C inhibition during CSF arrest. Fertilization triggers the Ca2+-dependent destruction of Emi2, releasing the APC/C to ubiquitinate the full pool of cyclin B and initiate completion of meiosis. Previously, we showed that a phosphatase maintains Emi2's APC/C-inhibitory activity in CSF-arrested Xenopus egg extracts. Here, we demonstrate that phosphatase inhibition permits Emi2 phosphorylation at thr-545 and -551, which inactivates Emi2. Furthermore, we provide evidence that adding excess cyclin B to CSF extracts stimulates Cdc2 phosphorylation of these same residues, antagonizing Emi2-APC/C association. Our findings suggest a model wherein the pool of Emi2 acts analogously to a rheostat by integrating Cdc2 and phosphatase activities to prevent cyclin B overaccumulation and Cdc2 hyperactivity during the indefinite period of time between arrival at metaphase II and eventual fertilization. Finally, we propose that inactivation of Emi2 by Cdc2 permits mitotic progression during early embryonic cleavage cycles.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Anaphase-Promoting Complex-Cyclosome
  • Animals
  • Cell Division / physiology
  • F-Box Proteins / antagonists & inhibitors
  • F-Box Proteins / metabolism
  • F-Box Proteins / physiology*
  • Female
  • Maturation-Promoting Factor / metabolism
  • Maturation-Promoting Factor / physiology*
  • Mice
  • Molecular Sequence Data
  • Oocytes
  • Proto-Oncogene Proteins c-mos / metabolism
  • Proto-Oncogene Proteins c-mos / physiology*
  • Ubiquitin-Protein Ligase Complexes / antagonists & inhibitors
  • Ubiquitin-Protein Ligase Complexes / metabolism
  • Ubiquitin-Protein Ligase Complexes / physiology
  • Xenopus Proteins / antagonists & inhibitors
  • Xenopus Proteins / metabolism
  • Xenopus Proteins / physiology*

Substances

  • F-Box Proteins
  • FBXO43 protein, Xenopus
  • Xenopus Proteins
  • Ubiquitin-Protein Ligase Complexes
  • Anaphase-Promoting Complex-Cyclosome
  • Proto-Oncogene Proteins c-mos
  • Maturation-Promoting Factor