Soluble components of Notch signalling can be applied to manipulate a central pathway essential for the development of metazoans and often deregulated in illnesses such as stroke, cancer or cardiovascular diseases. Commonly, the Notch cascade is inhibited by small compound inhibitors, which either block the proteolysis of Notch receptors by gamma-secretases or interfere with the transcriptional...

Delta/Notch-like EGF-related receptor (DNER) has been reported to act as a Notch ligand, despite lacking a Delta/Serrate/Lag (DSL) binding domain common to all other known ligands. The established Notch ligand Delta-like 1 (DLL1), but not DNER, activated Notch1 in a luciferase assay, prevented the differentiation of myoblasts through Notch signaling, and bound Notch-fc in a cell-based assay. DN...

The Notch family of proteins plays an integral role in determining cell fates, such as proliferation, differentiation, and apoptosis. We show that Notch-1 and its ligands, Delta-like-1 and Jagged-1, are overexpressed in many glioma cell lines and primary human gliomas. Immunohistochemistry of a primary human glioma tissue array shows the presence in the nucleus of the Notch-1 intracellular doma...

The Notch pathway is integrated into numerous developmental processes and therefore is fine-tuned on many levels, including receptor production, endocytosis, and degradation. Notch is further characterized by a twofold relationship with its Delta-Serrate (DSL) ligands, as ligands from opposing cells (trans-ligands) activate Notch, whereas ligands expressed in the same cell (cis-ligands) inhibit...

The Notch pathway is a highly conserved signaling system that controls a diversity of growth, differentiation, and patterning processes. In growing blood vessels, sprouting of endothelial tip cells is inhibited by Notch signaling, which is activated by binding of the Notch receptor to its ligand Delta-like 4 (Dll4). Here, we show that the Notch ligand Jagged1 is a potent proangiogenic regulator...

Endocytosis of the ligand delta; is required for activation of the receptor Notch during Drosophila development. The Notch extracellular domain (NotchECD) dissociates from the Notch intracellular domain (NotchICD) and is trans-endocytosed into delta;-expressing cells in wild-type imaginal discs. Reduction of dynamin-mediated endocytosis in developing eye and wing imaginal discs reduces Notch di...

Inhibition of Notch signaling by Numb is critical for many cell fate decisions. In this study, we demonstrate a more complex relationship between Notch and the two vertebrate Numb homologues Numb and Numblike. Although Numb and Numblike at low levels of Notch signaling negatively regulated Notch, high levels of Notch signaling conversely led to a reduction of Numb and Numblike protein levels in...

Fracture toughness (K1C) of medium carbon steel (0.5% C) has been determined by round notched tensile specimen. Two notch diameters (5.6mm and 4.2mm) and three notch angles (α) namely 45, 60 and 75 have been used to observe the effect of notch diameters and notch angle on fracture toughness of the steel. By heat treatment the microstructure of the steel is also varied and its effect on the frac...

OBJECTIVE Notch is known as a transmembranous receptor family with four homologous forms - Notch 1, Notch 2, Notch 3, and Notch 4 and related to cell fate regulation and angiogenesis. The purpose is to investigate the effect of follicular stimulating hormone (FSH) on the Notch 1 expression and proliferation in ovarian cancer cells. METHODS Human ovarian cancer cell line, SK-OV-3 and FSH were ...

Angiogenesis is essential for normal homeostasis, wound healing, and tumor growth and involves a switch in endothelial cell (EC) phenotype from quiescence to migration, proliferation and network formation, and back to quiescence. The notch signaling pathway is critically involved in cell fate decisions during development, and mice deficient in several notch/notch ligand genes have vascular phen...