The Notch signaling pathway: Transcriptional regulation at Notch target genes

By T. Borggrefe, F. Oswald. Cellular and Molecular Life Sciences, 2009

660 citations recorded by the source corpus.

Abstract.The Notch gene encodes a transmembrane receptor that gave the name to the evolutionary highly conserved Notch signaling cascade. It plays a pivotal role in the regulation of many fundamental cellular processes such as proliferation, stem cell maintenance and differentiation during embryonic and adult development. After specific ligand binding, the intracellular part of the Notch receptor is cleaved off and translocates to the nucleus, where it binds to the transcription factor RBP-J. In the absence of activated Notch, RBP-J represses Notch target genes by recruiting a corepressor complex. Here, we review Notch signaling with a focus on gene regulatory events at Notch target genes. This is of utmost importance to understand Notch signaling since certain RBP-J associated cofactors and particular epigenetic marks determine the specificity of Notch target gene expression in different cell types. We subsequently summarize the current knowledge about Notch target genes and the physiological significance of Notch signaling in development and cancer.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/180951110b6188d496224492384b145be99f0a23

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In Molecular Biology

1. T. Borggrefe
2. D. Tuveson
3. Michael Kühl
4. F. Oswald

Citations in the corpus

• iRegulon: From a Gene List to a Gene Regulatory Network Using Large Motif and Track Collections (2014, background): “that operate a perturbed gene network, and detecting their target genes, are instrumental steps in uncovering key insights into oncogenic programs, including the discovery of therapeutic targets [9–12].”
• A phospho-dependent mechanism involving NCoR and KMT2D controls a permissive chromatin state at Notch target genes (2016, background): “Although static binding of RBP-J has been challenged in Drosophila (14) and recently in a genome-wide study using a murine myoblast cell line (15), there is ample genetic and functional evidence for RBP-J acting as a transcriptional repressor (16,17).”
• A phase I trial of the γ-secretase inhibitor MK-0752 in combination with gemcitabine in patients with pancreatic ductal adenocarcinoma (2018, background): “The Notch pathway is involved in the development, differentiation, growth and fate of multiple different cell types (Bray, 2006), and has a fairly limited set of known target genes, including transcriptional regulators Hes (hairy/enhancer of split) and Hey (subfamily of Hes) (Borggrefe and Oswald, 2”