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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Blotting, Western
  • Cell Proliferation / drug effects
  • Cell Survival / genetics
  • Cell Survival / physiology*
  • Cells, Cultured
  • Endothelial Cells / cytology*
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism*
  • Humans
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Polymerase Chain Reaction
  • RNA, Small Interfering
  • Receptors, TNF-Related Apoptosis-Inducing Ligand / genetics
  • Receptors, TNF-Related Apoptosis-Inducing Ligand / metabolism
  • Vascular Endothelial Growth Factor A / pharmacology
  • fas Receptor / genetics
  • fas Receptor / metabolism


  • Nuclear Proteins
  • RNA, Small Interfering
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • fas Receptor