Fearnley, GW, Latham, AM, Hollstein, M et al. (2 more authors) (2020) ATF-2 and Tpl2 regulation of endothelial cell cycle progression and apoptosis. Cellular Signalling, 66. 109481. ISSN 0898-6568
Abstract
Cells respond to soluble and membrane-bound factors to activate signalling cascades that control cell proliferation and cell death. Vascular endothelial growth factor A (VEGF-A) is a soluble ligand that modulates a variety of cellular responses including cell proliferation and apoptosis. It is not well understood how VEGF-A signalling pathways regulate cell proliferation and cell death. To address this, we examined VEGF-A-regulated signalling pathways in the cytosol and nucleus and functional requirement for such cellular responses. The VEGF-A-regulated transcription factor, ATF-2, is required for cell cycle proteins such as p53, p21 and Cyclin D1. A cytosolic serine/threonine protein kinase (Tpl2) modulates ATF-2-regulated effects on the endothelial cell cycle. Such regulatory effects impact on endothelial cell proliferation, cell viability and apoptosis. These cellular effects influence complex cell-based organisation such as endothelial tubulogenesis. Our study now provides a framework for incorporating VEGF-A-stimulated signalling events from the cytosol to the nucleus which helps to understand how cell proliferation and apoptosis are controlled.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2019 Elsevier Inc. All rights reserved. This is an author produced version of a paper published in Cellular Signalling. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Signal transduction; Cell proliferation; Apoptosis; ATF-2; p53; Tpl2 |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) > Cardiovascular Science (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 17 Dec 2019 11:00 |
Last Modified: | 21 Nov 2020 01:39 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.cellsig.2019.109481 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:154696 |