Depletion of the novel protein PHACTR-1 from human endothelial cells abolishes tube formation and induces cell death receptor apoptosis
| Autor: | Ali Loukaci, Christiane Garbay, Yves Lepelletier, Réda Hadj-Slimane, Denis Biard, Lucia Borriello, Jérôme Larghero, Barbara Allain, Rafika Jarray, Françoise Raynaud |
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| Rok vydání: | 2011 |
| Předmět: |
Vascular Endothelial Growth Factor A
Cell Survival Blotting Western Apoptosis Biology Vascular endothelial growth inhibitor Biochemistry Polymerase Chain Reaction chemistry.chemical_compound Humans fas Receptor RNA Small Interfering S1PR1 Cells Cultured Cell Proliferation Tube formation Endothelial Cells Nuclear Proteins General Medicine Molecular biology Cell biology Vascular endothelial growth factor B Endothelial stem cell Vascular endothelial growth factor Vascular endothelial growth factor A Receptors TNF-Related Apoptosis-Inducing Ligand Vascular endothelial growth factor C chemistry |
| Zdroj: | Biochimie. 93(10) |
| ISSN: | 1638-6183 |
| Popis: | Using suppression subtractive hybridisation (SSH), we identified a hitherto unreported gene PHACTR-1 (Phosphatase Actin Regulating Protein-1) in Human Umbilical Vascular Endothelial Cells (HUVECs). PHACTR-1 is an actin and protein phosphatase 1 (PP1) binding protein which is reported to be highly expressed in brain and which controls PP1 activity and F-actin remodelling. We have also reported that its expression is dependent of Vascular Endothelial Growth Factor (VEGF-A 165 ). To study its function in endothelial cells, we used a siRNA strategy against PHACTR-1 . PHACTR-1 siRNA-treated HUVECs showed a major impairment of tube formation and stabilisation. PHACTR-1 depletion triggered apoptosis through death receptors DR4, DR5 and FAS, which was reversed using death receptor siRNAs or with death receptor-dependent caspase-8 siRNA. Our findings suggest that PHACTR-1 is likely to be a key regulator of endothelial cell function properties. Because of its central role in the control of tube formation and endothelial cell survival, PHACTR-1 may represent a new target for the development of anti-angiogenic therapy. |
| Databáze: | OpenAIRE |
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