hEcd, A Novel Regulator of Mammary Epithelial Cell Survival

TL;DRAbstract

Abstract : Using the Yeast Two hybrid analysis with human papilloma virus oncogene E6 (the most efficient oncogene to immortalize hMECs in vitro) as a bait and mammary epithelial cell cDNA library, we identified hEcd (human orthologue of Drosophila Ecdysoneless) as a novel E6 binding partner. To study the cellular function of Ecd in mammalian cells, we generated Ecd (lox/lox) mouse embryonic fibroblast cells from Ecd floxed mouse embryos (mice generation was not supported by DOD grant) . We observed that 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. Ecd directly bound to Rb at the pocket domain and competed with E2F for binding to hypophosphorylated Rb, demonstrating Ecd plays a role in cell cycle progression via the Rb-E2F pathway. Studies in yeast sug

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