Notch signaling pathway

The manifold effects of Notch are also attributed to interactions with other signalling pathways, which are still largely unexplained. The closest interactions have been found between the Notch and the EGF (epidermal growth factor) signalling pathway, which can be both agonistic and antagonistic in nature.

Notch is a transmembrane protein with a single transmembrane domain and a large extracellular domain. After ligand binding, the extracellular part is separated by a metalloprotease and the intracellular part of the receptor migrates into the cell nucleus and directly acts as a gene activator itself.

The intracellular counterpart of Notch is Hairless. The names of these signalling components are derived from the external appearance of fruit flies. Animals with a mutation in the hairless gene do not have bristles on their surface, whereas mutations in the Notch receptor result in characteristic notches in the area of the wing edge.

Notch1 regulates numerous processes in keratinocytes, such as cell differentiation, cell proliferation and apoptosis. Notch1 induces p21 Notch promotes the differentiation of embryonic keratinocytes and suppresses uninhibited proliferation. A deficiency of Notch 1 promotes the occurrence of squamous cell carcinomas. Notch 1 is diminished expressed in squamous cell carcinoma. UVA radiation has a negative influence on Notch 1 epxression.

Notch 1 protein is an essential factor in hematopoiesis for the differentiation of T lymphocytes and a general anti-apoptotic factor for T cells. In immature B cells, however, Notch1 has a rather proapoptotic and antiproliferative effect. Experimental data suggest that Notch1 is activated in antigen-stimulated mature B lymphocytes and has an inhibitory effect on both immunoglobulin secretion and the lifespan of activated B cells. The NOTCH1 gene shows mutations in about 50% of all acute T cell leukemias, which lead to permanent activation.