[Frontiers in Bioscience 14, 3619-3633, January 1, 2009]

Dipeptidyl peptidase 8 and 9 - guilty by association?

Melissa R. Pitman1, Melanie L. Sulda1,2, Bryone Kuss2, Catherine A. Abbott1

1School of Biological Sciences, Flinders University, GPO BOX 2100, Adelaide 5001, South Australia, Australia 2Department of Haematology and Genetic Pathology, Flinders Medical Centre, Bedford Park 5042, South Australia, Australia

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. DP gene structure and expression studies
4. Post-translational modifications of DP proteins
5. Structural elements of DP8/9: comparison to DPIV and FAP
6. Discovering potential DP8/9 substrates
7. Designing specific DP8/9 inhibitors to further elucidate their functional roles in vivo
8. Potential roles for DP8 and DP9
9. What the future holds for DP8 and DP9
10. References

1. ABSTRACT

Dipeptidyl peptidases (DP) 8 and 9 are members of the DPIV enzyme family. Other members include DPIV, fibroblast activation protein (FAP) and the non-enzymes DP6 and DP10. DPIV family members have diverse biological roles, and have been implicated in a range of diseases including diabetes, cancer, inflammatory bowel disease, multiple sclerosis (MS), arthritis and asthma. While DP8/9 biological functions are yet to be established, they have been predicted to have similar roles to the other DPs due to high sequence similarities within the active site of the enzymes. While there is mounting evidence towards the involvement of DP8 and/or DP9 in innate and acquired immunity, direct proof for the link between DP8 and DP9 and human disease is yet to be definitively shown, thus DP8 and 9 proteins remain guilty by association.