Regulation of the embryonic cell proliferation by Drosophila cyclin D and cyclin E complexes.
Cell proliferation during Drosophila development occurs in a well known spatial and temporal pattern which can readily be studied in vivo. The cells which form the larval epidermis exit from the cell division cycle during embryogenesis after the 16th round of mitosis when they enter for the first time into a G1/0 phase. We are interested in the mechanistic basis of this cell proliferation arrest. We have shown that the arrest requires the down-regulation of cyclin E/Cdk2 activity by inhibition of cyclin E expression and parallel activation of Dacapo/p27 expression. In addition, up-regulation of Fizzy-related is observed and is required for inhibition of Cdk1 activity. Do these processes result from the down-regulation of D-type cyclin/Cdk complexes? Extensive evidence from mammalian cells, and in particular from tumour cells has suggested that these complexes act as master regulators of cell proliferation upstream of cyclin E. Our genetic analyses indicate that Drosophila cyclin D/Cdk4, which interacts with the Drosophila Rb family member as expected, does not play an essential role in the regulation of cell proliferation.
Lehner
C F
CF
Department of Genetics, University of Bayreuth, 95447 Bayreuth, Germany.
Jacobs
H W
HW
Sauer
K
K
Meyer
C A
CA
D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins; D056741:Cyclin D; D019927:Cyclin E / Q000378:metabolism*; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism*; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000196:embryology* / Q000254:growth & development / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D009865:Oocytes / Q000502:physiology; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases; D011518:Proto-Oncogene Proteins
D018797:Cell Cycle Proteins; C534694:CycD protein, Drosophila; D056741:Cyclin D; D019927:Cyclin E; D016213:Cyclins; D029721:Drosophila Proteins; D004791:Enzyme Inhibitors; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C103336:dap protein, Drosophila; D016203:CDC2 Protein Kinase; C495896:Cdk4 protein, Drosophila; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases; D010749:Phosphoprotein Phosphatases; D017027:Protein Tyrosine Phosphatases; C059217:stg protein, Drosophila