Targeted Inactivation of Dipeptidyl Peptidase 9 Enzymatic Activity Causes Mouse Neonate Lethality

@article{Gall2013TargetedIO,
  title={Targeted Inactivation of Dipeptidyl Peptidase 9 Enzymatic Activity Causes Mouse Neonate Lethality},
  author={Margaret G. Gall and Yiqian Chen and Ana J{\'u}lia Vieira de Ribeiro and Hui Emma Zhang and Charles G Bailey and Derek Spielman and Denise Ming Tse Yu and Mark D. Gorrell},
  journal={PLoS ONE},
  year={2013},
  volume={8}
}
Dipeptidyl Peptidase (DPP) 4 and related dipeptidyl peptidases are emerging as current and potential therapeutic targets. DPP9 is an intracellular protease that is regulated by redox status and by SUMO1. DPP9 can influence antigen processing, epidermal growth factor (EGF)-mediated signaling and tumor biology. We made the first gene knock-in (gki) mouse with a serine to alanine point mutation at the DPP9 active site (S729A). Weaned heterozygote DPP9wt/S729A pups from 110 intercrosses were… 

Figures and Tables from this paper

Identification of novel dipeptidyl peptidase 9 substrates by two‐dimensional differential in‐gel electrophoresis
TLDR
This work identified the dipeptide Val‐Ala as a consensus site for DPP9 cleavage that was not recognized by DPP8, suggesting different in vivo roles for these closely related enzymes.
Expression, subcellular localisation, and possible roles of dipeptidyl peptidase 9 (DPP9) in murine macrophages
TLDR
Compared the messenger RNA expression profile of DPP9 to that of the related DPP8 and DPPIV in murine haematopoietic and lymphatic tissues and the colocalisation of D PP9 with endocytosed DQ‐OVA demonstrated in endosomes of J774 cells might suggest the role of DP9 in peptide processing within endosomal/vesicular compartment.
Pharmacology, Physiology, and Mechanisms of Action of Dipeptidyl Peptidase-4 Inhibitors
TLDR
The biology of DPP4 is reviewed with a focus on identification of pharmacological vs physiological DPP 4 substrates; and elucidation of mechanisms of actions of D PP4 in studies employing genetic elimination or chemical reduction ofDPP4 activity.
The Multifunctional Post-proline Dipeptidyl Peptidase, DPP9, in Mice, Cell Biology and Immunity
TLDR
Roles for DPP9 in regulating physiological and cellular processes, including immunity, metabolism and cancer, are supported by emerging data and derived from a genetically modified mouse strain and from manipulations of cell lines.
Dipeptidyl peptidase 9 substrates and their discovery: current progress and the application of mass spectrometry-based approaches
TLDR
A general overview of some tools and approaches available for protease substrate discovery and their applicability to the DPPs with a specific focus on DPP9 substrates is provided and comment upon potential approaches for future substrate elucidation is provided.
Dipeptidyl peptidase 9 triggers BRCA2 degradation by the N-degron pathway to promote DNA-damage repair
TLDR
DPP9 is identified as a regulator of BRCA2, providing a possible explanation for DPP9 involvement in cancer development.
Structures and mechanism of dipeptidyl peptidases 8 and 9, important players in cellular homeostasis and cancer
TLDR
Crystal and molecular structures of human DPP8 and DPP9, unliganded and complexed with a noncanonical substrate and a small molecule inhibitor, respectively are described, whereby a different active site architecture and substrate binding mechanism in this family is observed.
...
1
2
3
4
...

References

SHOWING 1-10 OF 68 REFERENCES
Cloning, expression and chromosomal localization of a novel human dipeptidyl peptidase (DPP) IV homolog, DPP8.
TLDR
DPP8, a novel human postproline dipeptidyl aminopeptidase that is homologous to DPPIV and FAP is described and a potential role for DPP8 in T-cell activation and immune function is suggested.
Advances in Understanding the Expression and Function of Dipeptidyl Peptidase 8 and 9
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
Enzyme Activity and Immunohistochemical Localization of Dipeptidyl Peptidase 8 and 9 in Male Reproductive Tissues
TLDR
The mRNA expression pattern of dipeptidyl peptidase (DPP) 8 and DPP9, two DPP4 homologs, was studied previously and showed a broad tissue distribution and was found associated with spermatozoids embedded in the epithelium, just before their release into the lumen, and in spermatids.
The In Vivo Expression of Dipeptidyl Peptidases 8 and 9
TLDR
DP8 and DP9 mRNA were ubiquitous in day 17 mouse embryo, with greatest expression in epithelium (skin and gastrointestinal tract) and brain, and their expression in lymphocytes and epithelia indicates potential for roles in the digestive and immune systems.
DPP8 and DPP9 expression in cynomolgus monkey and Sprague Dawley rat tissues
Dipeptidyl peptidase 9 (DPP9) from bovine testes: identification and characterization as the short form by mass spectrometry.
Dipeptidyl peptidase IV inhibition for the treatment of type 2 diabetes: potential importance of selectivity over dipeptidyl peptidases 8 and 9.
TLDR
Assessment of selectivity of potential clinical candidates may be important to an optimal safety profile for this new class of antihyperglycemic agents, according to the results of toxicity and tolerability studies.
Expression and enzymatic activity of dipeptidyl peptidase-IV in human astrocytic tumours are associated with tumour grade.
TLDR
This is the first report showing that non-malignant brain tissue contains a DPP-IV-like enzymatic activity, while the substantial part of the activity in glioma is due to increased D PP-IV/CD26, localized in both the vascular and parenchymal compartments.
...
1
2
3
4
5
...