The Conserved Kinases CDK-1, GSK-3, KIN-19, and MBK-2 Promote OMA-1 Destruction to Regulate the Oocyte-to-Embryo Transition in C. elegans

Curr Biol. 2006 Jan 10;16(1):47-55. doi: 10.1016/j.cub.2005.11.070. Epub 2005 Dec 15.

Abstract

Background: At the onset of embryogenesis, key developmental regulators called determinants are activated asymmetrically to specify the body axes and tissue layers. In C. elegans, this process is regulated in part by a conserved family of CCCH-type zinc finger proteins that specify the fates of early embryonic cells. The asymmetric localization of these and other determinants is regulated in early embryos through motor-dependent physical translocation as well as selective proteolysis.

Results: We show here that the CCCH-type zinc finger protein OMA-1 serves as a nexus for signals that regulate the transition from oogenesis to embryogenesis. While OMA-1 promotes oocyte maturation during meiosis, destruction of OMA-1 is needed during the first cell division for the initiation of ZIF-1-dependent proteolysis of cell-fate determinants. Mutations in four conserved protein kinase genes-mbk-2/Dyrk, kin-19/CK1alpha, gsk-3, and cdk-1/CDC2-cause stabilization of OMA-1 protein, and their phenotypes are partially suppressed by an oma-1 loss-of-function mutation. OMA-1 proteolysis also depends on Cyclin B3 and on a ZIF-1-independent CUL-2-based E3 ubiquitin ligase complex, as well as the CUL-2-interacting protein ZYG-11 and the Skp1-related proteins SKR-1 and SKR-2.

Conclusions: Our findings suggest that a CDK1/Cyclin B3-dependent activity links OMA-1 proteolysis to completion of the first cell cycle and support a model in which OMA-1 functions to prevent the premature activation of cell-fate determinants until after they are asymmetrically partitioned during the first mitosis.

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Animals
  • CDC2 Protein Kinase / metabolism
  • Caenorhabditis elegans / embryology*
  • Caenorhabditis elegans / enzymology*
  • Caenorhabditis elegans Proteins / metabolism*
  • Carrier Proteins / metabolism*
  • Cell Differentiation
  • Conserved Sequence
  • Embryo, Nonmammalian / cytology
  • Glycogen Synthase Kinase 3 / metabolism
  • Models, Biological
  • Molecular Sequence Data
  • Mutation
  • Nuclear Proteins / metabolism
  • Oocytes / cytology
  • Oocytes / enzymology*
  • Oocytes / growth & development*
  • Phosphorylation
  • Protein Kinases / metabolism*
  • Protein-Tyrosine Kinases / metabolism
  • Sequence Alignment
  • Signal Transduction
  • Wnt Proteins / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • Cks-1 protein, C elegans
  • Nuclear Proteins
  • OMA-1 protein, C elegans
  • Wnt Proteins
  • ZIF-1 protein, C elegans
  • pie-1 protein, C elegans
  • Protein Kinases
  • MBK-2 protein, C elegans
  • Protein-Tyrosine Kinases
  • KIN-19 protein, C elegans
  • CDC2 Protein Kinase
  • Glycogen Synthase Kinase 3