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NOTCH3DR

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Investigating a novel role of Notch3 as a dependence receptor and its relevance...

Investigating a novel role of Notch3 as a dependence receptor and its relevance in vivo Cell survival depends on the integration of numerous signals provided by the extracellular environment. Activation of signal transduction by transmembrane receptors is assumed to occur following interaction with a specific ligand.... ver más

31/08/2011

CLB

166K€

Presupuesto del proyecto: 166K€

Líder del proyecto

CENTRE DE LUTTE CONTRE LE CANCER LEON BERARD No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo FP7 notifico la concesión del proyecto el día 2011-08-31 No tenemos la información de la convocatoria

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Líder del proyecto

CENTRE DE LUTTE CONTRE LE CANCER LEON BERARD No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 166K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Cell survival depends on the integration of numerous signals provided by the extracellular environment. Activation of signal transduction by transmembrane receptors is assumed to occur following interaction with a specific ligand. However, some receptors, called dependence receptors (DRs) have been shown to mediate a signal in the absence of ligand. These receptors share the ability to mediate two opposing signals: in the presence of their cognate ligand, they transduce survival signals, whereas, in the absence of their ligand, they induce apoptosis. This idea was initially proposed for the Deleted in Colorectal Cancer (DCC) receptor, and now, number of such receptors has increased over the past ten years. There are now a dozen DRs described including the netrin-1 receptors DCC and UNC5H1-4, RET, TrkC, neogenin, and Patched. Identifying new dependence receptors is an important challenge since it causes a paradigm shift of a specific signalling pathway and alters our understanding of the developmental and physiological processes involving such receptors. For example, the DRs concept revealed a novel role for DCC in colon cancer, for netrin-1 in breast cancer metastasis and angiogenesis. Despite sharing little structural homology, all DRs contain a Dependence Associated Receptor Transmembrane (DART) motif, induce apoptosis in the absence of ligand and are cleaved by caspases to release a pro-apoptotic fragment. Preliminary data shows that Notch3 shares these characteristics. Notch3 is a member of the family of Notch receptors which regulates various stages in development and cancer as the receptors control cellular differentiation, proliferation and death. Notch3 has never been studied as a dependence receptor and the aim of this application is thus to further characterise Notch3 dependence signalling. We will study the mechanisms of Notch3-induced cell death and its relevance in physiological models, the involution of the mammary gland and lung cancers.

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