Induction of string rescues the neuroblast proliferation defect in trol mutant animals.
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.
Park
Youngji
Y
Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas 77843, USA.
Ng
Cristina
C
Datta
Sumana
S
D000483:Alleles; D000818:Animals; D042846:CDC2-CDC28 Kinases / Q000032:analysis; D018797:Cell Cycle Proteins; D002455:Cell Division; D019927:Cyclin E; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000032:analysis; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics*; D004627:Embryonic Induction; D005786:Gene Expression Regulation; D005982:Glutathione Transferase / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans / Q000235:genetics*; D006358:Hot Temperature; D007814:Larva / Q000378:metabolism; D009154:Mutation; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D017027:Protein Tyrosine Phosphatases; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016196:S Phase; D013997:Time Factors; D019076:Transgenes
D018797:Cell Cycle Proteins; D019927:Cyclin E; D029721:Drosophila Proteins; D019812:Heparan Sulfate Proteoglycans; D011993:Recombinant Fusion Proteins; C472788:trol protein, Drosophila; D005982:Glutathione Transferase; D042846:CDC2-CDC28 Kinases; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; C495887:cdk2 protein, Drosophila; D010749:Phosphoprotein Phosphatases; D017027:Protein Tyrosine Phosphatases; C059217:stg protein, Drosophila