ABIN-2 protects endothelial cells from death and has a role in the antiapoptotic effect of angiopoietin-1.
A20 binding inhibitor of NF-kappaB activation-2, ABIN-2, is a newly identified intracellular protein that interacts with the zinc finger protein A20. ABIN-2 inhibits nuclear factor-kappaB (NF-kappaB) activity and is a possible effector of A20 regulation of NF-kappaB. 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.
Tadros
Amir
A
University of Leicester, Dept Surgery, RKCSB, PO Box 65, Leicester, LE2 7LX, United Kingdom.
Hughes
David P
DP
Dunmore
Benjamin J
BJ
Brindle
Nicholas P J
NP
D048868:Adaptor Proteins, Signal Transducing; D000730:Androstadienes / Q000494:pharmacology; D042683:Angiopoietin-1 / Q000037:antagonists & inhibitors; D017209:Apoptosis / Q000502:physiology*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D042783:Endothelial Cells / Q000166:cytology; D004730:Endothelium, Vascular / Q000166:cytology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D042787:Receptor, TIE-2 / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D014162:Transfection; D000077191:Wortmannin
D048868:Adaptor Proteins, Signal Transducing; D000730:Androstadienes; D042683:Angiopoietin-1; D002352:Carrier Proteins; D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D042787:Receptor, TIE-2; D011993:Recombinant Fusion Proteins; D000077191:Wortmannin; C434062:TNIP2 protein, human; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one