DPP8 explained

Dipeptidyl peptidase 8 is an enzyme that in humans is encoded by the DPP8 gene.^{[1] [2]}

This gene encodes a member of the peptidase S9B family, a small family of dipeptidyl peptidases that are able to cleave peptide substrates at a prolyl bond. The encoded protein shares similarity with dipeptidyl peptidase-4 in that it is ubiquitously expressed, and hydrolyzes the same substrates. These similarities suggest that, like dipeptidyl peptidase IV, this protein may play a role in T-cell activation and immune function. Alternatively spliced transcript variants encoding different isoforms have been described. A relatively specific inhibitor of DPP8 and DPP9, Val-boroPro ^[3] -,^[4] leads to increased activation of the inflammasome though both NLRBP1 and CARD8 and can trigger pyroptosis.^[5]

References

Notes

Further reading

• Strausberg RL . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . vanc. Feingold EA . Grouse LH . 3 . Derge . JG . Klausner . RD . Collins . FS . Wagner . L . Shenmen . CM . Schuler . GD . 2002PNAS...9916899M . free .
• Ajami K . Structural requirements for catalysis, expression, and dimerization in the CD26/DPIV gene family . Biochemistry . 42 . 3 . 694–701 . 2003 . 12534281 . 10.1021/bi026846s . vanc. Abbott CA . Obradovic M . 3 . Gysbers . Vanessa . Kähne . Thilo . McCaughan . Geoffrey W. . Gorrell . Mark D. .
• Qi SY . Cloning and characterization of dipeptidyl peptidase 10, a new member of an emerging subgroup of serine proteases . Biochem. J. . 373 . Pt 1 . 179–89 . 2003 . 12662155 . 10.1042/BJ20021914 . 1223468 . vanc. Riviere PJ . Trojnar J . 3 . Junien . Jean-Louis . Akinsanya . Karen O. .
• Ota T . Complete sequencing and characterization of 21,243 full-length human cDNAs . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . vanc. Suzuki Y . Nishikawa T . 3 . Otsuki . Tetsuji . Sugiyama . Tomoyasu . Irie . Ryotaro . Wakamatsu . Ai . Hayashi . Koji . Sato . Hiroyuki . free .
• Shu H . Identification of phosphoproteins and their phosphorylation sites in the WEHI-231 B lymphoma cell line . Mol. Cell. Proteomics . 3 . 3 . 279–86 . 2004 . 14729942 . 10.1074/mcp.D300003-MCP200 . vanc. Chen S . Bi Q . 3 . Mumby . M . Brekken . DL . free .
• Chen YS . Purification and characterization of human prolyl dipeptidase DPP8 in Sf9 insect cells . Protein Expr. Purif. . 35 . 1 . 142–6 . 2004 . 15039077 . 10.1016/j.pep.2003.12.019 . vanc. Chien CH . Goparaju CM . 3 . Hsu . JT . Liang . PH . Chen . X .
• Gerhard DS . The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . vanc. Wagner L . Feingold EA . 3 . Shenmen . CM . Grouse . LH . Schuler . G . Klein . SL . Old . S . Rasooly . R .
• Jiaang WT . Novel isoindoline compounds for potent and selective inhibition of prolyl dipeptidase DPP8 . Bioorg. Med. Chem. Lett. . 15 . 3 . 687–91 . 2005 . 15664838 . 10.1016/j.bmcl.2004.11.023 . vanc. Chen YS . Hsu T . 3 . Wu . Ssu-Hui . Chien . Chia-Hui . Chang . Chung-Nien . Chang . Sheng-Ping . Lee . Shiow-Ju . Chen . Xin .
• Ogasawara W . Isoforms of dipeptidyl aminopeptidase IV from Pseudomonas sp. WO24: role of the signal sequence and overexpression in Escherichia coli . Protein Expr. Purif. . 41 . 2 . 241–51 . 2005 . 15866709 . 10.1016/j.pep.2004.10.027 . vanc. Tanaka C . Suzuki M . 3 . Kobayashi . G . Ogawa . Y . Okada . H . Morikawa . Y .
• Kimura K . Diversification of transcriptional modulation: Large-scale identification and characterization of putative alternative promoters of human genes . Genome Res. . 16 . 1 . 55–65 . 2006 . 16344560 . 10.1101/gr.4039406 . 1356129 . vanc. Wakamatsu A . Suzuki Y . 3 . Ota . T . Nishikawa . T . Yamashita . R . Yamamoto . J . Sekine . M . Tsuritani . K .
• Book: Yu DM . 575 . 63–72 . 2006 . 16700509 . 10.1007/0-387-32824-6_7 . vanc. Wang XM . Ajami K . 3 . Advances in Experimental Medicine and Biology . McCaughan . Geoffrey W. . Gorrell . Mark D. . Dipeptidyl Aminopeptidases . DP8 and DP9 have Extra-Enzymatic Roles in Cell Adhesion, Migration and Apoptosis . 978-0-387-29058-4 .
• Yu DM, Wang XM, McCaughan GW, Gorrell MD . Extraenzymatic functions of the dipeptidyl peptidase IV-related proteins DP8 and DP9 in cell adhesion, migration and apoptosis . FEBS J. . 273 . 11 . 2447–60 . 2006 . 16704418 . 10.1111/j.1742-4658.2006.05253.x . free .
• Lee HJ . Investigation of the dimer interface and substrate specificity of prolyl dipeptidase DPP8 . J. Biol. Chem. . 281 . 50 . 38653–62 . 2007 . 17040910 . 10.1074/jbc.M603895200 . vanc. Chen YS . Chou CY . 3 . Chien . C.-H. . Lin . C.-H. . Chang . G.-G. . Chen . X. . free .

Notes and References

1. Abbott CA, Yu DM, Woollatt E, Sutherland GR, McCaughan GW, Gorrell MD . Grant Robert Sutherland . Cloning, expression and chromosomal localization of a novel human dipeptidyl peptidase (DPP) IV homolog, DPP8 . Eur J Biochem . 267 . 20 . 6140–50 . Nov 2000 . 11012666 . 10.1046/j.1432-1327.2000.01617.x . free .
2. Web site: Entrez Gene: DPP8 dipeptidyl-peptidase 8.
3. Web site: PubChem:Val-boroPro.
4. Okondo MC, Rao SD, Taabazuing CY, Chui AJ, Poplawski SE, Johnson DC, Bachovchin DA . Inhibition of Dpp8/9 Activates the Nlrp1b Inflammasome . Cell Chemical Biology . 25 . 3 . 262–267.e5 . March 2018 . 29396289 . 5856610 . 10.1016/j.chembiol.2017.12.013 .
5. Johnson DC, Taabazuing CY, Okondo MC, Chui AJ, Rao SD, Brown FC, Reed C, Peguero E, de Stanchina E, Kentsis A, Bachovchin DA . DPP8/DPP9 inhibitor-induced pyroptosis for treatment of acute myeloid leukemia . Nature Medicine . 24 . 8 . 1151–1156 . August 2018 . 29967349 . 6082709 . 10.1038/s41591-018-0082-y .