notch2 signaling sensitizes endothelial cells to apoptosis by negatively regulating the key protective molecule survivinnotch2信号糖分会让内皮细胞凋亡的负调节的关键保护分子存活素.pdfVIP

Notch2 Signaling Sensitizes Endothelial Cells to Apoptosis by Negatively Regulating the Key Protective Molecule Survivin 1,2,3¤a 1,2,3 1,2,3 1,2,3 ´ ´ 4 Thibaut Quillard , Julie Devalliere , Mathias Chatelais , Flora Coulon , Celine Seveno , 4¤b ´ 4 ´ 1,2,3 Mathilde Romagnoli , Sophie Barille Nion , Beatrice Charreau * ´ ´ 1 INSERM, UMR643, Nantes, France, 2 CHU Nantes, Institut de Transplantation et de Recherche en Transplantation, ITERT, Nantes, France, 3 Universite de Nantes, Faculte ´ de Medecine, Nantes, France, 4 INSERM, UMR 892, Nantes, France Abstract Background: 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. Methodology/Principal Findings: 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 obtain