The Journal of biological chemistry
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.
Animals, Carrier Proteins, Cell Cycle, Cell Cycle Proteins, Cell Proliferation, Cells, Cultured, E2F1 Transcription Factor, Female, Fibroblasts, G1 Phase, Gene Expression, Humans, Immunoblotting, Immunoprecipitation, Male, Mice, Mice, Knockout, Mice, Transgenic, Phosphorylation, Protein Binding, Retinoblastoma Protein, S Phase, Time Factors
This research was originally published in The Journal of Biological Chemistry. Kim JH, Gurumurthy CB, Naramura M, et al. Role of mammalian Ecdysoneless in cell cycle regulation. The Journal of Biological Chemistry.v 2009; 284: 26402-10. © the American Society for Biochemistry and Molecular Biology.
Kim, Jun Hyun; Gurumurthy, Channabasavaiah B.; Naramura, Mayumi; Zhang, Ying; Dudley, Andrew T.; Doglio, Lynn; Band, Hamid; and Band, Vimla, "Role of mammalian Ecdysoneless in cell cycle regulation." (2009). Journal Articles: Genetics, Cell Biology & Anatomy. Paper 26.