Physiology and pathology of notch signalling system

Abstract

Notch proteins encode a family of transmembrane receptors that are part of a signalling transduction system known as Notch signalling, an extremely conserved and widely used mechanism regulating programs governing growth, apoptosis and differentiation in metazoans. Notch signalling begins when the Notch receptor binds ligands and ends when the Notch intracellular domain enters the nucleus and activates transcription of target genes. This core pathway is subjected to a wide array of regulatory influences and protein-protein interactions and is correlated with other signalling pathway. This review will sumarize recent findings concerning the physiology and pathology of Notch signalling in vascular development and homeostasis. Moreover, the clinical phenotypes of Notch3 signalling system pathology will be described, with particular regard to CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) for which the most recent pathogenetic hypotheses are reported.

Tumor-Initiating Cells of HER2-Positive Carcinoma Cell Lines Express the Highest Oncoprotein Levels and Are Sensitive to Trastuzumab

“…Spheres derived from MDA-MB-361, SKOV-3, BT-474, and ZR-75-1 expressed higher levels of Notch1 intracellular domain compared with the spheres grown on matrigel (from 1.6 to 1.3 folds). Hes1, a known Notch1 target gene (27,28), was up-regulated in the spheres of the four cell lines, thus confirming the activation of Notch1 in tumorinitiating cells (Fig. 3A).…”

Expression profiling of rat mammary epithelial cells reveals candidate signaling pathways in dietary protection from mammary tumors

“…Sfrp2 is a soluble form of the Wnt receptor frizzled and, by binding Wnts, prevents the activation of the Wnt signaling pathway and the nuclear accumulation of ␤-catenin (66). Notch2, a member of a family of growth regulatory proteins (6), is found at high levels in cells undergoing metaplastic/neoplastic transformations (3) and is involved in the maintenance of undifferentiated epithelial cells (19). In breast cancer cell lines, Hes1 functions as a negative regulator of estrogen-dependent proliferation, with its expression negatively correlated with that of the proliferative marker PCNA (58).…”

A role for Notch signaling in trophoblast endovascular invasion and in the pathogenesis of pre-eclampsia

“…The Notch signaling pathway governs differentiation and function during cell-cell contact in many tissues (Bianchi et al, 2006;Miele, 2006) with particularly important roles in vascular patterning (Roca and Adams, 2007;Swift and Weinstein, 2009). Mechanistically, Notch receptors operate both on the cell surface to receive activating signals and within the nucleus as transcriptional modulators (Alva and Iruela-Arispe, 2004;Kopan and Ilagan, 2009).…”