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Transcriptional Regulation Of Vegf-A By The Unfolded Protein Response Pathway, Rajarshi Ghosh, Kathryn L. Lipson, Karen E. Sargent, Arthur M. Mercurio, Joan S. Hunt, David Ron, Fumihiko Urano
Transcriptional Regulation Of Vegf-A By The Unfolded Protein Response Pathway, Rajarshi Ghosh, Kathryn L. Lipson, Karen E. Sargent, Arthur M. Mercurio, Joan S. Hunt, David Ron, Fumihiko Urano
Arthur M. Mercurio
BACKGROUND: Angiogenesis is crucial to many physiological and pathological processes including development and cancer cell survival. Vascular endothelial growth factor-A (VEGFA) is the predominant mediator of angiogenesis in the VEGF family. During development, adverse environmental conditions like nutrient deprivation, hypoxia and increased protein secretion occur. IRE1alpha, PERK, and ATF6alpha, master regulators of the unfolded protein response (UPR), are activated under these conditions and are proposed to have a role in mediating angiogenesis. PRINCIPAL FINDINGS: Here we show that IRE1alpha, PERK, and ATF6alpha powerfully regulate VEGFA mRNA expression under various stress conditions. In Ire1alpha(-/-) and Perk(-/-) mouse embryonic fibroblasts and ATF6alpha-knockdown …