Dipeptidyl peptidase (DPP) 8 is a member of the DPP4/DPP-IV gene and enzyme family, which belongs to clan SC of serine proteases, family S9, subfamily S9B. S9B proteases have a unique ability to remove Xaa-Pro dipeptides from the N-terminus of substrates. Fibroblast activation protein (FAP), DPP4, DPP8, and DPP9 are the S9B peptidases. Several extensive reviews provide detail (Zhang et al. 2013; Waumans et al. 2015; Klemann et al. 2016; Wilson et al. 2016).
DPP8 has been localized to human chromosome 15q22.32 (Abbott et al. 2000) and 9:65032458 in the mouse. The human DPP8 gene spans 71 kb and comprises 20 exons (Abbott et al. 2000), which is shorter and with fewer exons than DPP4 but encodes more amino acids (882 versus 766 residues). In DPP8 and DPP9, the gene sequence encoding the catalytic serine and its nearby highly conserved amino acids is in a single exon, whereas in...
KeywordsDPP8 Inhibitor Ewing Sarcoma Gastric Inhibitory Polypeptide Dipeptidyl Peptidase Nuclear Localization Sequence
MDG is supported by grants 1105238 and 1113842 from the Australian National Health and Medical Research Council.
- Ajami K, Pitman MR, Wilson CH, Park J, Menz RI, Starr AE, et al. Stromal cell-derived factors 1 alpha and 1 beta, inflammatory protein-10 and interferon-inducible T cell chemo-attractant are novel substrates of dipeptidyl peptidase 8. FEBS Lett. 2008;582:819–25. doi: 10.1016/j.febslet.2008.02.005.CrossRefPubMedGoogle Scholar
- Geiss-Friedlander R, Parmentier N, Moeller U, Urlaub H, Van den Eynde BJ, Melchior F. The cytoplasmic peptidase DPP9 is rate-limiting for degradation of proline-containing peptides. J Biol Chem. 2009;284:27211–9. doi: 10.1074/jbc.M109.041871.
- Justa-Schuch D, Möller U, Geiss-Friedlander R. The amino terminus extension in the long dipeptidyl peptidase 9 isoform contains a nuclear localization signal targeting the active peptidase to the nucleus. Cell Mol Life Sci. 2014;71:3611–26. doi: 10.1007/s00018-014-1591-6.CrossRefPubMedGoogle Scholar
- Walsh MP, Duncan B, Larabee S, Krauss A, Davis JP, Cui Y, et al. Val-BoroPro accelerates T cell priming via modulation of dendritic cell trafficking resulting in complete regression of established murine tumors. PLoS One. 2013;8:e58860. doi: 10.1371/journal.pone.0058860.CrossRefPubMedPubMedCentralGoogle Scholar
- Waumans Y, Baerts L, Kehoe K, Lambeir A-M, De Meester I. The dipeptidyl peptidase family, prolyl oligopeptidase and prolyl carboxypeptidase in the immune system and inflammatory disease, including atherosclerosis. Front Immunol. 2015;6:387–405. doi: 10.3389/fimmu.2015.00387.CrossRefPubMedPubMedCentralGoogle Scholar
- Wilson CH, Indarto D, Doucet A, Pogson LD, Pitman MR, Menz RI, et al. Identifying natural substrates for dipeptidyl peptidase 8 (DP8) and DP9 using terminal amine isotopic labelling of substrates, TAILS, reveals in vivo roles in cellular homeostasis and energy metabolism. J Biol Chem. 2013;288:13936–49. doi: 10.1074/jbc.M112.445841.CrossRefPubMedPubMedCentralGoogle Scholar
- Wu W, Liu Y, Milo Jr LJ, Shu Y, Zhao P, Li Y, et al. 4-Substituted boro-proline dipeptides: synthesis, characterization, and dipeptidyl peptidase IV, 8, and 9 activities. Bioorg Med Chem Lett 2012;22:5536–5540. 10.1016/j.bmcl.2012.07.033.