[Frontiers in Bioscience S3, 1232-1262, June 1, 2011]

The importance of Ca2+/Zn2+ signaling S100 proteins and RAGE in translational medicine

Estelle Leclerc1, Claus W. Heizmann2

1Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58108, USA, 2Department of Pediatrics, Division of Clinical Chemistry and Biochemistry, University of Zurich, Steinwiesstrasse 75, 8032 Zurich, Switzerland


1. Abstract
2. Introduction
3. General features of S100 proteins
4. The receptor for advanced glycation endproducts (RAGE)
5. Structures and functions of S100 proteins and RAGE: association with human pathologies
5.1. S100B
5.2. S100A1
5.3. S100A2
5.4. S100A3
5.5. S100A4
5.6. S100A5
5.7. S100A6
5.8. S100A7
5.9. S100A7L1
5.10. S100A8/A9
5.11. S100A10
5.12. S100A11
5.13. S100A12
5.14. S100A13
5.15. S100A14
5.16. S100A16
5.17. S100G
5.18. S100P
5.19. S100Z
6. Complexity of RAGE/S100 interaction
7. RAGE/S100 in human diseases and therapeutic approaches
8. Conclusion
9. Acknowledgement
10. References


The Receptor for Advanced Glycation Endproducts (RAGE) is a multiligand receptor involved in a large number of human disorders. Identified first as the receptor for the Advanced Glycation Endproducts (AGEs), RAGE has emerged in recent years as a major receptor for many members of the S100 calcium and zinc binding protein family. The interaction with and the signaling triggered by several S100 proteins such as S100B and S100A12 have been studied in details and have shown concentration and cell type dependent signaling cascades. The S100 protein family consists of more than 20 members which present high amino-acid sequence and structural similarities. These small EF-hand calcium binding proteins interact with a large number of protein targets and are almost all been shown to be involved in cancer. In this review we discuss the recent knowledge about the role of S100 proteins and RAGE in human disorders.