Induction of string rescues the neuroblast proliferation defect in trol mutant animals

Genesis. 2003 Aug;36(4):187-95. doi: 10.1002/gene.10216.

Abstract

In trol mutants, neuroblasts fail to exit G1 for S phase. Increasing string expression in trol mutants rescues the number of S phase neuroblasts without an increase in M phase neuroblasts. Decreasing string expression further decreased the number of S phase neuroblasts. Coexpression of cyclin E and string did not produce additional S phase cells. Unlike cyclin E, cdk2, and cdk2AF, elevated expression of neither cyclin A, cyclin D, nor cdk1AF was able to promote S phase progression in arrested neuroblasts, indicating that String-induced activity of a Cyclin A or Cyclin D complex is unlikely to drive trol neuroblasts into S phase. Biochemical analyses revealed a rapid increase of Cyclin E-Cdk2 kinase activity to wild-type levels upon increased string expression. These results suggest that Drosophila Cdc25 may directly or indirectly increase the kinase activity of Cyclin E-Cdk2 complexes in vivo, thus driving arrested neuroblasts into cell division.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Animals
  • CDC2-CDC28 Kinases / analysis
  • Cell Cycle Proteins
  • Cell Division
  • Cyclin E
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinases / analysis
  • Drosophila
  • Drosophila Proteins / genetics*
  • Embryonic Induction*
  • Gene Expression Regulation
  • Glutathione Transferase / metabolism
  • Heparan Sulfate Proteoglycans / genetics*
  • Hot Temperature
  • Larva / metabolism
  • Mutation
  • Neurons / cytology
  • Neurons / physiology*
  • Phosphoprotein Phosphatases / metabolism*
  • Protein Tyrosine Phosphatases*
  • Recombinant Fusion Proteins / metabolism
  • S Phase
  • Time Factors
  • Transgenes

Substances

  • Cell Cycle Proteins
  • Cyclin E
  • Drosophila Proteins
  • Heparan Sulfate Proteoglycans
  • Recombinant Fusion Proteins
  • trol protein, Drosophila
  • Glutathione Transferase
  • CDC2-CDC28 Kinases
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinases
  • cdk2 protein, Drosophila
  • Phosphoprotein Phosphatases
  • Protein Tyrosine Phosphatases
  • stg protein, Drosophila