Regulation of the lymphatic endothelial cell cycle by the PROX1 homeodomain protein
| Autor: | David Cheung, Hae K. Kim, Shunzhen Zhang, Josette M. Douville, Shannon A. Baxter, David D. Eisenstat, Patricia Bocangel, Krista L. Herbert, Jaganmohan Reddy Jangamreddy, Jeffrey T. Wigle |
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| Rok vydání: | 2010 |
| Předmět: |
Umbilical Veins
Cyclin E Endothelium government.form_of_government Cyclin A Cyclin E1 Blotting Western Apoptosis Kidney Immunoenzyme Techniques Mice medicine Animals Humans Lymphatic endothelial cell RNA Small Interfering Luciferases Promoter Regions Genetic Transcription factor Molecular Biology Cells Cultured Cell Proliferation Homeodomain Proteins Binding Sites biology Tumor Suppressor Proteins Cell Cycle Endothelial Cells Cell Biology Cell cycle Molecular biology Cell biology Endothelial stem cell Lymphatic Endothelium medicine.anatomical_structure Vascular endothelial growth factor C biology.protein government Endothelium Vascular Transcription E2F1 Transcription Factor |
| Zdroj: | Biochimica et biophysica acta. 1813(1) |
| ISSN: | 0006-3002 |
| Popis: | The homeobox transcription factor PROX1 is essential for the development and maintenance of lymphatic vasculature. How PROX1 regulates lymphatic endothelial cell fate remains undefined. PROX1 has been shown to upregulate the expression of Cyclin E, which mediates the G1 to S transition of the cell cycle. Here we demonstrate that PROX1 activates the mouse Cyclin E1 (Ccne1) promoter via two proximal E2F-binding sites. We have determined that the N-terminal region of PROX1 is sufficient to activate a 1-kb Ccne1 promoter, whereas the homeodomain is dispensable for activation. We have identified that the Prospero domain 1 (PD1) is required for the nuclear localization of PROX1. Our comparison of two DNA-binding-deficient constructs of PROX1 showed a cell-type-specific difference between these two proteins in both their localization and function. We demonstrated that siRNA-mediated knockdown of PROX1 in lymphatic endothelial cells decreases progression from G1 to S phase of the cell cycle. We conclude that PROX1 activates the Ccne1 promoter independent of DNA binding, and our results illustrate a novel role for PROX1 in the regulation of lymphatic endothelial cell proliferation. |
| Databáze: | OpenAIRE |
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