Ets1 and Ets2 are required for endothelial cell survival during embryonic angiogenesis
AUTOR(ES)
Wei, Guo
FONTE
American Society of Hematology
RESUMO
The ras/Raf/Mek/Erk pathway plays a central role in coordinating endothelial cell activities during angiogenesis. Transcription factors Ets1 and Ets2 are targets of ras/Erk signaling pathways that have been implicated in endothelial cell function in vitro, but their precise role in vascular formation and function in vivo remains ill-defined. In this work, mutation of both Ets1 and Ets2 resulted in embryonic lethality at midgestation, with striking defects in vascular branching having been observed. The action of these factors was endothelial cell autonomous as demonstrated using Cre/loxP technology. Analysis of Ets1/Ets2 target genes in isolated embryonic endothelial cells demonstrated down-regulation of Mmp9, Bcl-XL, and cIAP2 in double mutants versus controls, and chromatin immunoprecipitation revealed that both Ets1 and Ets2 were loaded at target promoters. Consistent with these observations, endothelial cell apoptosis was significantly increased both in vivo and in vitro when both Ets1 and Ets2 were mutated. These results establish essential and overlapping functions for Ets1 and Ets2 in coordinating endothelial cell functions with survival during embryonic angiogenesis.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2721789Documentos Relacionados
- Reciprocal expression of human ETS1 and ETS2 genes during T-cell activation: regulatory role for the protooncogene ETS1.
- Ets1 is required for p53 transcriptional activity in UV-induced apoptosis in embryonic stem cells
- Signal-Transducing Adaptor Molecules STAM1 and STAM2 Are Required for T-Cell Development and Survival
- Definition of an Ets1 protein domain required for nuclear localization in cells and DNA-binding activity in vitro.
- Inhibition of endothelial cell survival and angiogenesis by protein kinase A