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The Notch‐regulated ankyrin repeat protein (Nrarp) is a component of a negative feedback system that attenuates Notch pathway‐mediated signaling. In vertebrates, the timing and spacing of formation of the mesodermal somites are controlled by a molecular oscillator termed the segmentation clock. Somites are also patterned along the rostral‐caudal axis of the embryo. Here, we demonstrate that Nrarp‐deficient...
We have identified a gene encoding a novel protein that is transcriptionally regulated by the Notch signaling pathway in mammals. This gene, named Nrarp (for Notch-regulated ankyrin-repeat protein), encodes a 114 amino acid protein that has a unique amino-terminus and a carboxy-terminal domain containing two ankyrin-repeat motifs. A Xenopus homolog of the Nrarp gene was previously identified in a...
Notch proteins regulate many developmental processes. Notch1 is highly expressed on thymocytes, but its role in regulating their development is not known. We show that activation of Notch1 signaling in CD4 + CD8 + double positive thymocytes promotes the maturation of both CD4 + and CD8 + single positive thymocytes and that this occurs in the absence of interactions...
We have identified RORγt, a novel, thymus-specific isoform of the orphan nuclear receptor RORγ that is expressed predominantly in CD4 + CD8 + double-positive thymocytes. Ectopic expression of RORγt protects T cell hybridomas from activation-induced cell death by inhibiting the upregulation of Fas ligand. Following hybridoma stimulation, RORγt also inhibits IL-2 production but does...
The Notch receptor and its ligands are involved in many developmental processes. They are highly expressed in the thymus and have been implicated in the CD4 versus CD8 lineage decision. We identified the constitutively active intracellular fragment of murine Notch-1 as capable of rendering thymomas resistant to glucocorticoid-induced apoptosis. This effect was confirmed in other T cell lines and in...
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