Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Stromblad, S; Becker, JC; Yebra, M; Brooks, PC; Cheresh, DA.
Suppression of p53 activity and p21(WAF1/CIP1) expression by vascular cell integrin alpha v beta 3 during angiogenesis
J CLIN INVEST. 1996; 98(2): 426-433.
Doi: 10.1172/JCI118808
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- Co-Autor*innen der Med Uni Graz
- Becker Jürgen Christian
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- Abstract:
- Induction of p53 activity in cells undergoing DNA synthesis represents a molecular conflict that can lead to apoptosis. During angiogenesis, proliferative endothelial cells become apoptotic in response to antagonists of integrin alpha v beta 3 and this leads to the regression of angiogenic blood vessels, thereby blocking the growth of various human tumors. Evidence is presented that administration of alpha v beta 3 antagonists during angiogenesis in vivo selectively caused activation of endothelial cell p53 and increased expression of the p53-inducible cell cycle inhibitor p21(WAF1/CIP1). In vitro studies revealed that the ligation state of human endothelial cell alpha v beta 3 directly influenced p53 activity and the bax cell death pathway. Specifically, agonists of endothelial cell alpha v beta 3, but not other integrins, suppressed p53 activity, blocked p21(WAF1/CIP1) expression, and increased the bcl-2/bax ratio, thereby promoting cell survival. Thus, ligation of vascular cell integrin alpha v beta 3 promotes a critical and specific adhesion-dependent cell survival signal during angiogenesis leading to inhibition of p53 activity, decreased expression of p21(WAF1/CIP1), and suppression of the bax cell death pathway.
- Find related publications in this database (Keywords)
- gene expression
- apoptosis
- cell cycle
- bcl-2