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Prepublished online as a Blood First Edition Paper on August 21, 2003; DOI 10.1182/blood-2003-05-1602.

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2003-05-1602v1
102/13/4407    most recent
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Submitted May 19, 2003
Accepted August 18, 2003

ABIN-2 protects endothelial cells from death and has a role in the anti-apoptotic effect of angiopoietin-1

Amir Tadros, David P Hughes, Benjamin J Dunmore, and Nicholas P J Brindle*

Department of Surgery, University of Leicester, Leicester, United Kingdom

* Corresponding author; email: npjb1{at}leicester.ac.uk.

A20 binding inhibitor of NFkB activation-2, ABIN-2, is a newly identified intracellular protein that interacts with the zinc finger protein A20. ABIN-2 inhibits NFkB activity and is a possible effector of A20 regulation of NFkB. Although A20 is a potent inhibitor of endothelial apoptosis, the effect of ABIN-2 on apoptosis is not known. ABIN-2 also interacts with the endothelial receptor Tie2. This receptor is essential for blood vessel formation and promotes endothelial survival. Here we examine the effects of ABIN-2 on endothelial cell apoptosis and its potential involvement in Tie2-mediated endothelial survival. ABIN-2 was found to inhibit endothelial apoptosis and rescue cells from death following growth factor-deprivation. The inhibitors of phosphatidylinositol 3-kinase, wortmannin and LY294002, suppressed ABIN-2 inhibition of endothelial cell death. Deletion of the carboxy-terminus of ABIN-2 removed its ability to inhibit apoptosis. Expression of truncated ABIN-2 prevented the Tie2 activating ligand angiopoietin-1 from inhibiting endothelial cell death.


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