Molecular Mechanisms of Notch Signaling

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.

Contenu

Preface

Contributors

Part 1 Introduction 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