Role of mammalian Ecdysoneless in cell cycle regulation.
The Ecdysoneless (Ecd) protein is required for cell-autonomous roles in development and oogenesis in Drosophila, but the function of its evolutionarily conserved mammalian orthologs is not clear. To study the cellular function of Ecd in mammalian cells, we generated Ecd(lox/lox) mouse embryonic fibroblast cells from Ecd floxed mouse embryos. Cre-mediated deletion of Ecd in Ecd(lox/lox) mouse embryonic fibroblasts led to a proliferative block due to a delay in G(1)-S cell cycle progression; this defect was reversed by the introduction of human Ecd. Loss of Ecd led to marked down-regulation of E2F target gene expression. Furthermore, Ecd directly bound to Rb at the pocket domain and competed with E2F for binding to hypophosphorylated Rb. Our results demonstrate that mammalian Ecd plays a role in cell cycle progression via the Rb-E2F pathway.
Kim
Jun Hyun
JH
Department of Genetics, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198-5805, USA.
Gurumurthy
Channabasavaiah Basavaraju
CB
Naramura
Mayumi
M
Zhang
Ying
Y
Dudley
Andrew T
AT
Doglio
Lynn
L
Band
Hamid
H
Band
Vimla
V
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D050687:E2F1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D016193:G1 Phase / Q000502:physiology; D015870:Gene Expression; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010766:Phosphorylation; D011485:Protein Binding; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism; D016196:S Phase / Q000502:physiology; D013997:Time Factors
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D050687:E2F1 Transcription Factor; C513410:ECD protein, human; D016160:Retinoblastoma Protein