CSL-Associated Corepressor and Coactivator Complexes

Advances in Experimental Medicine and Biology
Franz Oswald, Rhett A Kovall

Abstract

The highly conserved Notch signal transduction pathway orchestrates fundamental cellular processes including, differentiation, proliferation, and apoptosis during embryonic development and in the adult organism. Dysregulated Notch signaling underlies the etiology of a variety of human diseases, such as certain types of cancers, developmental disorders and cardiovascular disease. Ligand binding induces proteolytic cleavage of the Notch receptor and nuclear translocation of the Notch intracellular domain (NICD), which forms a ternary complex with the transcription factor CSL and the coactivator MAML to upregulate transcription of Notch target genes. The DNA-binding protein CSL is the centrepiece of transcriptional regulation in the Notch pathway, acting as a molecular hub for interactions with either corepressors or coactivators to repress or activate, respectively, transcription. Here we review previous structure-function studies of CSL-associated coregulator complexes and discuss the molecular insights gleaned from this research. We discuss the functional consequences of both activating and repressing binding partners using the same interaction platforms on CSL. We also emphasize that although there has been a significant uptic...Continue Reading

Citations

Dec 31, 2019·Development, Growth & Differentiation·Julia Falo-Sanjuan, Sarah J Bray
Sep 24, 2019·Experimental Biology and Medicine·Daniel P Hall, Rhett A Kovall
Feb 3, 2019·Development·Domingos Henrique, François Schweisguth

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