CDC-25.1 controls the rate of germline mitotic cell cycle by counteracting WEE-1.3 and by positively regulating CDK-1 in Caenorhabditis elegans

Cell Cycle. 2012 Apr 1;11(7):1354-63. doi: 10.4161/cc.19755. Epub 2012 Apr 1.

Abstract

In Caenorhabditis elegans, cdc-25.1 loss-of-function mutants display a lack of germline proliferation. We found that the proliferation defect of cdc-25.1 mutants was suppressed by wee-1.3 RNAi. Further, among the seven cdk and seven cyclin homologs examined, cdk-1 and cyb-3 RNAi treatment caused the most severe germline proliferation defects in an rrf-1 mutant background, which were similar to those of the cdc-25.1 mutants. In addition, while RNAi of cyd-1 and cye-1 caused significant germline proliferation defects, RNAi of cdk-2 and cdk-4 did not. Compared with the number of germ nuclei in wee-1.3(RNAi) worms, the number in wee-1.3(RNAi);cdk-1(RNAi) and wee-1.3(RNAi);cyb-3(RNAi) worms further decreased to the level of cdk-1(RNAi) and cyb-3(RNAi) worms, respectively, indicating that cdk-1 and cyb-3 are epistatic and function downstream of cdc-25.1 and wee-1.3 in the control of the cell cycle. BrdU labeling of adult worms showed that, while 100% of the wild-type germ nuclei in the mitotic region incorporated BrdU when labeled for more than 12 h at 20°C, a small fraction of the cdc-25.1 mutant germ nuclei failed to incorporate BrdU even when labeled for 68 h. These results indicate that CDC-25.1 is required for maintaining proper rate of germline mitotic cell cycle. We propose that CDC-25.1 regulates the rate of germline mitotic cell cycle by counteracting WEE-1.3 and by positively controlling CDK-1, which forms a complex primarily with CYB-3, but also possibly with CYD-1 and CYE-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CDC2 Protein Kinase / genetics
  • CDC2 Protein Kinase / metabolism*
  • Caenorhabditis elegans / cytology
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cell Cycle Proteins / genetics
  • Cell Cycle* / genetics
  • Cell Division
  • Cyclin B / genetics
  • Cyclin B / metabolism
  • Cyclin-Dependent Kinase 2 / genetics
  • Cyclin-Dependent Kinase 2 / metabolism
  • Cyclin-Dependent Kinase 4 / genetics
  • Cyclin-Dependent Kinase 4 / metabolism
  • Germ Cells / physiology*
  • Mitosis* / genetics
  • Mutation
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism*
  • RNA Interference
  • RNA, Small Interfering
  • cdc25 Phosphatases / metabolism*

Substances

  • CYB-3 protein, C elegans
  • Caenorhabditis elegans Proteins
  • Cell Cycle Proteins
  • Cyclin B
  • RNA, Small Interfering
  • cyd-1 protein, C elegans
  • wee-1.3 protein, C elegans
  • Protein-Tyrosine Kinases
  • Protein-Serine-Threonine Kinases
  • CDC2 Protein Kinase
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinase 4
  • CDC-25.1 protein, C elegans
  • cdc25 Phosphatases