G1 cyclin-dependent kinases are insufficient to reverse dE2F2-mediated repression.
Here we show that the cell cycle defects of dE2F1-depleted cells depend on the cooperative effects of dE2F2 and DACAPO (DAP), an inhibitor of Cyclin E/cyclin-dependent kinase 2 (CycE/cdk2). The different properties of cells lacking dE2F1/dE2F2 and dE2F1/DAP lead to the surprising observation that dE2F2-mediated repression differs from retinoblastoma family protein 1 (RBF1) inhibition of dE2F1, and is resistant to both CycE/cdk2 and Cyclin D/cyclin-dependent kinase 4 (CycD/cdk4). This resistance occurs even though dE2F2/RBF1 complexes are disrupted by CycE/cdk2, and may explain why dE2F2 is so potent in the absence of de2f1. The implication of these results is that cells containing dE2F2 require dE2F1 to either prevent, or reverse, dE2F-mediated repression.
Frolov
Maxim V
MV
Massachusetts General Hospital Cancer Center, Charlestown, MA 02129, USA.
Stevaux
Olivier
O
Moon
Nam-Sung
NS
Dimova
Dessislava
D
Kwon
Eun-Jeong
EJ
Morris
Erick J
EJ
Dyson
Nicholas J
NJ
D000483:Alleles; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D042846:CDC2-CDC28 Kinases; D002453:Cell Cycle; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism; D019927:Cyclin E / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004330:Drosophila; D029721:Drosophila Proteins; D050703:E2F2 Transcription Factor; D016193:G1 Phase; D008156:Luciferases / Q000378:metabolism; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism; D011233:Precipitin Tests; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D034622:RNA Interference; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection
D002843:Chromatin; D019927:Cyclin E; D029721:Drosophila Proteins; D050703:E2F2 Transcription Factor; C115434:E2f2 protein, Drosophila; D009687:Nuclear Proteins; D014157:Transcription Factors; C103336:dap protein, Drosophila; D008156:Luciferases; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; C495887:cdk2 protein, Drosophila