1. Introduction to Molecular Mechanisms in Notch Signal Transduction and Disease Pathogenesis
Benedetto Daniele Giaimo and Tilman Borggrefe
Part 2 – Molecular mechanisms of receptor/ligand interactions
2. Structural insights into Notch receptor-ligand interactions
Penny Handford, Boguslawa Korona, Richard Suckling, Christina Redfield and Susan Lea
3. The Molecular Mechanism of Notch Activation
Klaus N. Lovendahl, Stephen C. Blacklow and Wendy R. Gordon
4. Regulation of Notch Function by O-Glycosylation
Beth M. Harvey and Robert S. Haltiwanger
5. Modeling the Notch response
Udi Binshtok and David Sprinzak
6. Endocytic trafficking of the Notch receptor
Björn Schnute, Tobias Troost and Thomas Klein
Part 3 – Intracellular signaling mechanisms
7. The Notch Interactome: complexity in signaling circuitry
Diana M. Ho, K. G. Guruharsha and Spyros Artavanis-Tsakonas
8. Integration of Drosophila and Human Genetics to understand Notch signaling related diseases
Shinya Yamamoto and Jose L. Salazar
9. Mechanisms of non-canonical signaling in health and disease: Diversity to take therapy up a Notch?
Victor Alfred and Thomas Vaccari
10. The Notch3 receptor and its intracellular signaling-dependent oncogenic mechanisms
Diana Bellavia, Saula Checquolo, Rocco Palermo and Isabella Screpanti
11. Notch and neurogenesis
Anna Engler, Runrui Zhang and Verdon Taylor
12. Notch and stem cells
Anna Bigas and Cristina Porcheri
13. Oscillatory control of Notch signaling in development
Ryoichiro Kageyama, Hiromi Shimojo and Akihiro Isomura
14. CSL-associated corepressor and coactivator complexes
Franz Oswald and Rhett A. Kovall
Part 4 – Disease links and therapeutics
15. Notch and senescence
Matthew Hoare and Masashi Narita
16. Control of blood vessel formation by Notch signaling
Fabian Tetzlaff and Andreas Fischer
17. Notch and T cell function – a complex tale
Jyothi Vijayaraghavan and Barbara A. Osborne
18. Notch in leukemia
Anna C. Gormley, Qing Wang and Mark Chiangs
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 useful resource 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.