Pro-apoptotic BIM is an essential initiator of physiological endothelial cell death independent of regulation by FOXO3
Publication Year 2014-06-27, Volume 21, Issue #11, Page 1687-1695
Journal Title
Cell Death Differ
Publication Type
Journal Article
The growth of new blood vessels by angiogenesis is essential for normal development, but can also cause or contribute to the pathology of numerous diseases. Recent studies have shown that BIM, a pro-apoptotic BCL2-family protein, is required for endothelial cell apoptosis in vivo, and can contribute to the anti-angiogenic effect of VEGF-A inhibitors in certain tumor models. Despite its importance, the extent to which BIM is autonomously required for physiological endothelial apoptosis remains unknown and its regulation under such conditions is poorly defined. While the transcription factor FOXO3 has been proposed to induce Bim in response to growth factor withdrawal, evidence for this function is circumstantial. We report that apoptosis was reduced in Bim-/- primary endothelial cells, demonstrating a cell-autonomous role for BIM in endothelial death following serum and growth factor withdrawal. In conflict with in vitro studies, BIM-dependent endothelial death in vivo did not require FOXO3. Moreover, endothelial apoptosis proceeded normally in mice lacking FOXO-binding sites in the Bim promoter. Bim mRNA was upregulated in endothelial cells starved of serum and growth factors and this was accompanied by the downregulation of miRNAs of the miR-17 approximately 92 cluster. Bim mRNA levels were also elevated in miR-17 approximately 92+/- endothelial cells cultured under steady-state conditions, suggesting that miR-17 approximately 92 cluster miRNAs may contribute to regulating overall Bim mRNA levels in endothelial cells.Cell Death and Differentiation advance online publication, 27 June 2014; doi:10.1038/cdd.2014.90.
WEHI Research Division(s)
Molecular Genetics Of Cancer; Molecular Medicine; Development And Cancer
Rights Notice
Refer to copyright notice on published article.

Creation Date: 2014-06-30 08:31:35
Last Modified: 2015-03-25 04:24:22
An error has occurred. This application may no longer respond until reloaded. Reload 🗙