DPP9 in a nutshell
Dipeptidyl peptidase 9 (DPP9), an intracellular serine protease, has recently been identified as a key player in pro-inflammatory cell death and regulation of the innate immune response. Similar to its closest family members DPP4 and DPP8, it cleaves a dipeptide after proline from the N-terminus of its substrates. Despite the high degree of similarity between the enzymes, DPP9 is gaining interest in the fields of immunology and cancer biology. What makes DPP9 particularly interesting is the fact that it regulates cytokine signalling by immune cells, it complexes with the regulating protein SUMO1 and DPP8/9 inhibitors activate an inflammasome-related pattern recognition receptor in human and rodent immune cells. As DPP9 appears to orchestrate important aspects of cellular biology, focussing on this remarkable enzyme may lead to the discovery of novel landmarks in human immunology.
Why do we study DPP9?
In our lab, DPP9 evolved from just one of the DPP4-family members to an important and interesting research topic during the investigation of the pleiotropic effects of therapeutically used DPP4 inhibitors. We were surprised to discover that not DPP4 but both DPP8 and DPP9 are abundantly present in macrophage-rich regions of atherosclerotic plaques which are, by definition, highly inflammatory sites. Additional studies in human myeloid-derived macrophages served as stimulation and inspiration to extensively dissect the role DPP9 in these phagocytes.
We contribute to the thriving field of DPP9 research by combining a broad range of expertise with the specific know-how we gained over decades studying various serine proteases. An important aspect we are currently exploring is the effect of DPP9 inhibition on cytokine expression and viability of human myeloid-derived macrophages. Additionally, we aim to identify novel interaction partners of DPP9 in macrophages and subsequently characterize these interactions. These studies may all serve as valuable tools to unravel the biochemistry of DPP9. In this regard, we can explore the potential of DPP9 to become a valuable pharmacological target in for instance cancer and auto-immunity.
Literature
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