Historical Background
Dipeptidyl peptidase (DPP) 9 is a member of the DPP4 (DPP-IV) family, which are all members of 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) and DPP8 are the other S9B peptidases.
DPP9 has been localized to human chromosome 19p13.3 (Olsen and Wagtmann 2002). The human DPP9 gene spans 48.6 kb and comprises 22 exons that are 53 bp to 1431 bp in length (Ajami et al. 2004). A predominant DPP9 mRNA transcript of 4.4 kb (AY374518; encoding 863 amino acids, the short form) is ubiquitous, with the highest levels in liver, heart, and skeletal muscle (Olsen and Wagtmann 2002; Ajami et al. 2004). A less abundant 5 kb transcript (AF542510; encoding 971 amino acids) that is abundant in skeletal muscle contains a second ATG translation start site that...
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Ajami K, Abbott CA, McCaughan GW, Gorrell MD. Dipeptidyl peptidase 9 has two forms, a broad tissue distribution, cytoplasmic localization and DPIV-like peptidase activity. Biochim Biophys Acta. 2004;1679:18–28. https://doi.org/10.1016/j.bbaexp.2004.03.010.
Chen Y, Gall MG, Zhang H, Keane FM, McCaughan GW, Yu DM, et al. Dipeptidyl peptidase 9 enzymatic activity influences the expression of neonatal metabolic genes. Exp Cell Res. 2016;342:72–82. https://doi.org/10.1016/j.yexcr.2016.02.020.
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. https://doi.org/10.1074/jbc.M109.041871.
Han R, Wang X, Bachovchin W, Zukowska Z, Osborn JW. Inhibition of dipeptidyl peptidase 8/9 impairs preadipocyte differentiation. Sci Rep. 2015;5:12348. https://doi.org/10.1038/srep12348. http://www.nature.com/articles/srep12348-supplementary-information
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. https://doi.org/10.1007/s00018-014-1591-6.
Olsen C, Wagtmann N. Identification and characterization of human Dpp9, a novel homologue of dipeptidyl peptidase IV. Gene. 2002;299:185–93.
Pilla E, Kilisch M, Lenz C, Urlaub H, Geiss-Friedlander R. The SUMO1-E67 interacting loop peptide is an allosteric inhibitor of the dipeptidyl peptidases 8 and 9. J Biol Chem. 2013;288:32787–96. https://doi.org/10.1074/jbc.M113.489179.
Spagnuolo PA, Hurren R, Gronda M, Maclean N, Datti A, Basheer A, et al. Inhibition of intracellular dipeptidyl peptidases 8 and 9 enhances parthenolide’s anti-leukemic activity. Leukemia. 2013;27:1236–44. https://doi.org/10.1038/leu.2013.9.
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. https://doi.org/10.1371/journal.pone.0058860.
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. https://doi.org/10.3389/fimmu.2015.00387.
Waumans Y, Vliegen G, Maes L, Rombouts M, Declerck K, Veken PVD, et al. The dipeptidyl peptidases 4, 8, and 9 in mouse monocytes and macrophages: DPP8/9 inhibition attenuates M1 macrophage activation in mice. Inflammation. 2016;39:413–24. https://doi.org/10.1007/s10753-015-0263-5.
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. https://doi.org/10.1074/jbc.M112.445841.
Wilson CH, Zhang HE, Gorrell MD, Abbott CA. Dipeptidyl peptidase substrate discovery: current progress and the application of mass spectrometry – based approaches. Biol Chem. 2016;397:837–56. https://doi.org/10.1515/hsz-2016-0174.
Wu J-J, Tang H-K, Yeh T-K, Chen C-M, Shy H-S, Chu Y-R, et al. Biochemistry, pharmacokinetics, and toxicology of a potent and selective DPP8/9 inhibitor. Biochem Pharmacol. 2009;78:203–10. https://doi.org/10.1016/j.bcp.2009.03.032.
Yao T-W, Kim W-S, Yu DM, Sharbeen G, McCaughan GW, Choi K-Y, et al. A novel role of dipeptidyl peptidase 9 in epidermal growth factor signaling. Mol Cancer Res. 2011;9:948–59. https://doi.org/10.1158/1541-7786.MCR-10-0272.
Yu DMT, Wang XM, McCaughan GW, Gorrell MD. Extra-enzymatic functions of the dipeptidyl peptidase (DP) IV related proteins DP8 and DP9 in cell adhesion, migration and apoptosis. FEBS J. 2006;273:2447–61.
Yu DMT, Ajami K, Gall MG, Park J, Lee CS, Evans KA, et al. The in vivo expression of dipeptidyl peptidases 8 and 9. J Histochem Cytochem. 2009;57:1025–40. https://doi.org/10.1369/jhc.2009.953760.
Zhang H, Chen Y, Keane FM, Gorrell MD. Advances in understanding the expression and function of dipeptidyl peptidase 8 and 9. Mol Cancer Res. 2013;11:1487–96. https://doi.org/10.1158/1541-7786.mcr-13-0272.
Zhang H, Chen Y, Wadham C, McCaughan GW, Keane FM, Gorrell MD. Dipeptidyl peptidase 9 subcellular localization and a role in cell adhesion involving focal adhesion kinase and paxillin. Biochim Biophys Acta. 2015a;1853:470–80. https://doi.org/10.1016/j.bbamcr.2014.11.029.
Zhang H, Maqsudi S, Rainczuk A, Duffield N, Lawrence J, Keane FM, et al. Identification of novel dipeptidyl peptidase 9 substrates by two-dimensional differential in-gel electrophoresis. FEBS J. 2015b;282:3737–57. https://doi.org/10.1111/febs.13371.
Acknowledgment
MDG is supported by grants 1105238 and 1113842 from the Australian National Health and Medical Research Council.
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Zhang, H.E., Gorrell, M.D. (2018). DPP9. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_101597
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DOI: https://doi.org/10.1007/978-3-319-67199-4_101597
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