Molecular Mechanisms of Notch Signaling, 1st ed. 2018 Advances in Experimental Medicine and Biology Series, Vol. 1066

This book describes the Notch signaling pathway with a focus on molecular mechanisms. The Notch signaling pathway is a seemingly simple pathway that does not involve any second messenger. Upon ligand binding two consecutive proteolytic cleavages of the NOTCH receptor release the Notch intracellular domain from the membrane. The Notch intracellular domain migrates into the nucleus and activates gene expression.

Recently, new technologies allowed us to better understand this pivotal signaling cascade and revealed new regulatory mechanisms. The different chapters cover many aspects of the Notch signaling focusing on the mechanisms governing the receptor/ligand interaction as well as on the downstream intracellular signaling events. Aspects of both canonical and non-canonical signaling are discussed and the function of Notch signaling in physiological and pathological contexts are elucidated.

This book is not only intended for experts but it should also be a usefulresource for young, sprouting scientists or interested scientists from other research areas, who may use this book as a stimulating starting point for further discoveries and developments.

Introduction to Molecular Mechanisms in Notch Signal Transduction and Disease Pathogenesis.- Structural insights into Notch receptor-ligand interactions.- The Molecular Mechanism of Notch Activation.- Regulation of Notch Function by O-Glycosylation.- Modeling the Notch response.- Endocytic trafficking of the Notch receptor.- The Notch Interactome: complexity in signaling circuitry.- Integration of Drosophila and Human Genetics to understand Notch signaling related diseases.- Mechanisms of non-canonical signaling in health and disease: Diversity to take therapy up a Notch?.- The Notch3 receptor and its intracellular signaling-dependent oncogenic mechanisms.- Notch and neurogenesis.- Notch and stem cells.- Oscillatory control of Notch signaling in development.- CSL-associated corepressor and coactivator complexes.- Notch and senescence.- Control of blood vessel formation by Notch signaling.- Notch and T cell function – a complex tale.- Notch in leukemia.