title: Advances in understanding the expression and function of dipeptidyl peptidase 8 and 9.
abstract: DPP8 and DPP9 are recently identified members of the dipeptidyl peptidase IV (DPPIV) enzyme family, which is characterized by the rare ability to cleave a post-proline bond two residues from the N-terminus of a substrate. DPP8 and DPP9 have unique cellular localization patterns, are ubiquitously expressed in tissues and cell lines, and evidence suggests important contributions to various biological processes including: cell behavior, cancer biology, disease pathogenesis, and immune responses. Importantly, functional differences between these two proteins have emerged, such as DPP8 may be more associated with gut inflammation whereas DPP9 is involved in antigen presentation and intracellular signaling. Similarly, the DPP9 connections with H-Ras and SUMO1, and its role in AKT1 pathway downregulation provide essential insights into the molecular mechanisms of DPP9 action. The recent discovery of novel natural substrates of DPP8 and DPP9 highlights the potential role of these proteases in energy metabolism and homeostasis. This review focuses on the recent progress made with these post-proline dipeptidyl peptidases and underscores their emerging importance.
authors.affiliation: Molecular Hepatology, Centenary Institute, Locked Bag No. 6, Newtown, NSW 2042, Australia. m.gorrell@centenary.usyd.edu.au.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Yiqian
authors.initials: Y
authors.lastname: Chen
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Keane
authors.forename: Mark D
authors.initials: MD
authors.lastname: Gorrell
mesh_terms: D000818:Animals; D020134:Catalytic Domain; D004150:Dipeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018819:Dipeptidyl Peptidase 4 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004734:Energy Metabolism; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D013379:Substrate Specificity
chemical_list: D004150:Dipeptidases; C471241:DPP9 protein, human; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C487997:DPP8 protein, human; D018819:Dipeptidyl Peptidase 4