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The Multifunctional Post-proline Dipeptidyl Peptidase, DPP9, in Mice, Cell Biology and Immunity

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Pathophysiological Aspects of Proteases

Abstract

Dipeptidyl peptidase 9 (DPP9) is a ubiquitous intracellular post-proline protease of the DPP4 (S9b) family of atypical serine proteases. Emerging data support roles for DPP9 in intracellular signalling, particularly in the epidermal growth factor receptor pathway, in immune cells, particularly in macrophages and antigen processing, and in energy metabolism. The focus of this review is the roles of DPP9 in regulating physiological and cellular processes. Such data is derived from a genetically modified mouse strain and from manipulations of cell lines. The mouse strain that lacks DPP9 enzyme activity is homozygous lethal. DPP9 alters behaviours, such as cell adhesion, of cancer cell lines. This review points to the functional importance of DPP9 in immunity, metabolism and cancer.

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Abbreviations

AMC:

Amino methylcoumarin

AMPK:

AMP-activated protein kinase

B-CLL:

B-cell chronic lymphocytic leukaemia

CAF:

Cancer-associated fibroblasts

CXCL:

CXC chemokine ligand

DEN:

Diethylnitrosamine

DPP:

Dipeptidyl peptidase

DSS:

Dextran sulphate sodium

DTT:

Dithiothreitol

ECM:

Extracellular matrix

EGF:

Epidermal growth factor

EGFR:

Epidermal growth factor receptor

EMT:

Epithelial–mesenchymal transition

ESFT:

Ewing sarcoma family of tumours

FAP:

Fibroblast activation protein

FGF:

Fibroblast growth factor

HCC:

Hepatocellular carcinoma

HFD:

High fat diet

HSC:

Hepatic stellate cells

IRS:

Insulin receptor substrate

IκBα:

Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha

MMP:

Matrix metalloproteinase

NEM:

N-ethylmaleimide

NPY:

Neuropeptide Y

PARP:

Poly(ADP-ribose) polymerase

PGC-1α:

PPAR coactivator-1α

PBMC:

Peripheral blood mononuclear cells

pNA:

P-nitroaniline

POP:

Prolyl oligopeptidase

PPAR:

Peroxisome proliferator-activated receptor

SUMO:

Small ubiquitin-like modifier

TAA:

Thioacetamide

TAM:

Tumour-associated macrophages

TGF:

Transforming growth factor

TNF-α:

Tumour necrosis factor α

VEGF-A:

Vascular endothelial growth factor-A

WT:

Wild-type

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Acknowledgements

This work was supported by National Health and Medical Research Council of Australia Project Grants 512282 and 1113842 (MDG), and a Sydney Medical School Foundation/Francis M. Hooper Scholarship for Medical Research through the University of Sydney (MGG).

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  1. Centenary Institute and Sydney Medical School, University of Sydney, Sydney, NSW, 2042, Australia

    Margaret G. Gall & Mark D. Gorrell

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  1. Margaret G. Gall
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  2. Mark D. Gorrell
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Correspondence to Mark D. Gorrell .

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  1. Department of Biochemistry and Biophysics, University of Kalyani, Kalyani, West Bengal, India

    Sajal Chakraborti

  2. Institute of Cardiovascular Sciences, University of Manitoba, Manitoba, Canada

    Naranjan S. Dhalla

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Gall, M.G., Gorrell, M.D. (2017). The Multifunctional Post-proline Dipeptidyl Peptidase, DPP9, in Mice, Cell Biology and Immunity. In: Chakraborti, S., Dhalla, N. (eds) Pathophysiological Aspects of Proteases. Springer, Singapore. https://doi.org/10.1007/978-981-10-6141-7_2

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