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Biochimie. 2011 Oct;93(10):1668-75. doi: 10.1016/j.biochi.2011.07.010. Epub 2011 Jul 26.

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

Author information

1
Université Paris Descartes, Sorbonne Paris Cité, CNRS UMR 8601, Laboratoire de chimie et biochimie pharmacologiques et toxicologiques, 45 rue des Saints-Pères, 75006 Paris, France.

Abstract

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.

PMID:
21798305
DOI:
10.1016/j.biochi.2011.07.010
[Indexed for MEDLINE]

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