Endothelial cell survival during angiogenesis requires the pro-survival protein MCL1
- Author(s)
- Watson, EC; Whitehead, L; Adams, RH; Dewson, G; Coultas, L;
- Details
- Publication Year 2016-08,Volume 23,Issue #8,Page 1371-1379
- Journal Title
- Cell Death and Differentiation
- Publication Type
- Journal Article
- Abstract
- Angiogenesis is essential to match the size of blood vessel networks to the metabolic demands of growing tissues. While many genes and pathways necessary for regulating angiogenesis have been identified, those responsible for endothelial cell (EC) survival during angiogenesis remain largely unknown. We have investigated the in vivo role of myeloid cell leukemia 1 (MCL1), a pro-survival member of the BCL2 family, in EC survival during angiogenesis. EC-specific deletion of Mcl1 resulted in a dose-dependent increase in EC apoptosis in the angiogenic vasculature and a corresponding decline in vessel density. Our results suggest this apoptosis was independent of the BH3-only protein BIM. Despite the known link between apoptosis and blood vessel regression, this was not the cause of reduced vessel density observed in the absence of endothelial MCL1. Rather, the reduction in vessel density was linked to ectopic apoptosis in regions of the angiogenic vasculature where EC proliferation and new vessel growth occurs. We have therefore identified MCL1 as an essential survival factor for ECs that is required for blood vessel production during angiogenesis.Cell Death and Differentiation advance online publication, 4 March 2016; doi:10.1038/cdd.2016.20.
- Publisher
- NPG
- Research Division(s)
- Development And Cancer; Cell Signalling And Cell Death
- PubMed ID
- 26943318
- Link To PubMed Central Version
- https://www-ncbi-nlm-nih-gov/pmc/articles/PMC4947668/
- Publisher's Version
- https://doi.org/10.1038/cdd.2016.20
- NHMRC Grants
- NHMRC/1010638,
- ARC Grants
- ARC/FT110100891, ARC/FT100100791,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2016-03-15 03:47:48
Last Modified: 2018-01-11 10:31:22