Notch2 signaling sensitizes endothelial cells to apoptosis by negatively regulating the key protective molecule survivin.

<h4>Background</h4>Notch signaling pathway controls key functions in vascular and endothelial cells (ECs) where Notch4 plays a major role. However, little is known about the contribution of other Notch receptors. This study investigated regulation of Notch2 and further examined its impli...

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Autores principales:	Thibaut Quillard, Julie Devalliere, Mathias Chatelais, Flora Coulon, Céline Séveno, Mathilde Romagnoli, Sophie Barillé Nion, Béatrice Charreau
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7caf26718e3240c4830bb410734886a2
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spelling	oai:doaj.org-article:7caf26718e3240c4830bb410734886a22021-11-25T06:27:29ZNotch2 signaling sensitizes endothelial cells to apoptosis by negatively regulating the key protective molecule survivin.1932-620310.1371/journal.pone.0008244https://doaj.org/article/7caf26718e3240c4830bb410734886a22009-12-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20011512/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Notch signaling pathway controls key functions in vascular and endothelial cells (ECs) where Notch4 plays a major role. However, little is known about the contribution of other Notch receptors. This study investigated regulation of Notch2 and further examined its implication in EC dysfunction.<h4>Methodology/principal findings</h4>Here, we provide evidence for a novel link between Notch and TNF signaling, where Notch2 is upregulated and activated in response to TNF. Forced expression of Notch2 intracellular domain in cultured ECs promotes apoptosis and allows the significant downregulation of several cell-death-related transcripts in a dose-dependent manner. In particular, activation of Notch2 led to a rapid decrease in survivin mRNA and protein expression, while survivin upregulation was obtained by the selective knockdown of Notch2 in ECs, indicating that survivin expression is controlled at the Notch level. Moreover, Notch2 silencing and ectopic expression of survivin, but not XIAP or Bcl2, rescued ECs from TNF and Notch2-mediated apoptosis, respectively.<h4>Conclusions/significance</h4>In conclusion, TNF signaling activates Notch2 that sensitizes ECs to apoptosis via modulation of the key apoptosis regulator survivin. Overall, our findings also indicate that specific Notch receptors control distinct functions in vascular cells and inflammatory cytokines contribute to this specificity.Thibaut QuillardJulie DevalliereMathias ChatelaisFlora CoulonCéline SévenoMathilde RomagnoliSophie Barillé NionBéatrice CharreauPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 12, p e8244 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Thibaut Quillard Julie Devalliere Mathias Chatelais Flora Coulon Céline Séveno Mathilde Romagnoli Sophie Barillé Nion Béatrice Charreau Notch2 signaling sensitizes endothelial cells to apoptosis by negatively regulating the key protective molecule survivin.
description	<h4>Background</h4>Notch signaling pathway controls key functions in vascular and endothelial cells (ECs) where Notch4 plays a major role. However, little is known about the contribution of other Notch receptors. This study investigated regulation of Notch2 and further examined its implication in EC dysfunction.<h4>Methodology/principal findings</h4>Here, we provide evidence for a novel link between Notch and TNF signaling, where Notch2 is upregulated and activated in response to TNF. Forced expression of Notch2 intracellular domain in cultured ECs promotes apoptosis and allows the significant downregulation of several cell-death-related transcripts in a dose-dependent manner. In particular, activation of Notch2 led to a rapid decrease in survivin mRNA and protein expression, while survivin upregulation was obtained by the selective knockdown of Notch2 in ECs, indicating that survivin expression is controlled at the Notch level. Moreover, Notch2 silencing and ectopic expression of survivin, but not XIAP or Bcl2, rescued ECs from TNF and Notch2-mediated apoptosis, respectively.<h4>Conclusions/significance</h4>In conclusion, TNF signaling activates Notch2 that sensitizes ECs to apoptosis via modulation of the key apoptosis regulator survivin. Overall, our findings also indicate that specific Notch receptors control distinct functions in vascular cells and inflammatory cytokines contribute to this specificity.
format	article
author	Thibaut Quillard Julie Devalliere Mathias Chatelais Flora Coulon Céline Séveno Mathilde Romagnoli Sophie Barillé Nion Béatrice Charreau
author_facet	Thibaut Quillard Julie Devalliere Mathias Chatelais Flora Coulon Céline Séveno Mathilde Romagnoli Sophie Barillé Nion Béatrice Charreau
author_sort	Thibaut Quillard
title	Notch2 signaling sensitizes endothelial cells to apoptosis by negatively regulating the key protective molecule survivin.
title_short	Notch2 signaling sensitizes endothelial cells to apoptosis by negatively regulating the key protective molecule survivin.
title_full	Notch2 signaling sensitizes endothelial cells to apoptosis by negatively regulating the key protective molecule survivin.
title_fullStr	Notch2 signaling sensitizes endothelial cells to apoptosis by negatively regulating the key protective molecule survivin.
title_full_unstemmed	Notch2 signaling sensitizes endothelial cells to apoptosis by negatively regulating the key protective molecule survivin.
title_sort	notch2 signaling sensitizes endothelial cells to apoptosis by negatively regulating the key protective molecule survivin.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/7caf26718e3240c4830bb410734886a2
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Notch2 signaling sensitizes endothelial cells to apoptosis by negatively regulating the key protective molecule survivin.

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