Depletion of the novel protein PHACTR-1 from human endothelial cells abolishes tube formation and induces cell death receptor apoptosis

作者：Jarray Rafika; Allain Barbara; Borriello Lucia; Biard Denis; Loukaci Ali; Larghero Jerome; Hadj Slimane Reda; Garbay Christiane; Lepelletier Yves; Raynaud Francoise^*

来源：Biochimie, 2011, 93(10): 1668-1675.

DOI：10.1016/j.biochi.2011.07.010

• PHACTR-1
• Tube formation
• Cell death receptor apoptosis
• siRNA

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.

• 出版日期2011-10
• 单位中国地震局