Dipeptidyl peptidase II (DPPII), a review

Maes, Marie-Berthe; Scharpé, Simon; Meester, Ingrid De

doi:10.1016/j.cca.2007.01.024

Cited by 68 publications

(55 citation statements)

References 168 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…To identify the non-T cell and non-B cell populations, FACS analysis was further performed. The percentage of Ter-119 ϩ /CD45 ϩ erythroid lineage cells in the spleen was dramatically increased in the AEP-null mice (e.g., 18.2% in a representative AEP-null mouse compared with just 0.4% in a wild-type control) (Fig. 3B).…”

Section: Resultsmentioning

confidence: 94%

“…Presumably, protease activities in AEP erythrocytes are impaired, leading to abnormal membrane protein destruction during the erythrocyte development. Indeed, activity of dipeptidyl peptidase II, a protease that can be found in erythrocytes in which activity depends on the maturation status (18), is dramatically elevated in AEP-null tissues (19). The defective RBCs were actively engulfed by the histiocytes in the spleen and bone marrow, which might explain why the RBC count was evidently decreased in AEP-null mice.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Mice lacking asparaginyl endopeptidase develop disorders resembling hemophagocytic syndrome

Chan

Abe

Hashimoto

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Asparaginyl endopeptidase (AEP or legumain) is a lysosomal cysteine protease that cleaves protein substrates on the C-terminal side of asparagine. AEP plays a pivotal role in the endosome/lysosomal degradation system and is implicated in antigen processing. The processing of the lysosomal proteases cathepsins in kidney is completely defective in AEP-deficient mice with accumulation of macromolecules in the lysosomes, which is typically seen in lysosomal disorders. Here we show that mutant mice lacking AEP develop fever, cytopenia, hepatosplenomegaly, and hemophagocytosis, which are primary pathological manifestations of hemophagocytic syndrome/hemophagocytic lymphohistiocytosis (HLH). Moreover, AEP deficiency provokes extramedullary hematopoiesis in the spleen and abnormally enlarged histiocytes with ingested red blood cells (RBCs) in bone marrow. Interestingly, RBCs from AEP-null mice are defective in plasma membrane components. Further, AEP-null mice display lower natural killer cell activity, but none of the major cytokines is substantially abnormal. These results indicate that AEP might be a previously unrecognized component in HLH pathophysiology.

show abstract

Section: Resultsmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Mice lacking asparaginyl endopeptidase develop disorders resembling hemophagocytic syndrome

Chan

Abe

Hashimoto

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Other potentially confounding proteases with DPP activity such as DPP 8, DPP 9, and DPP2 are primarily cytosolic and not known to be secreted. 37 FAP and DPP-IV cleave a penultimate alanine or proline from the N terminus of the substrate. To determine the degree of DPP activity inhibited by Val-boroPro, we analyzed exopeptidase activity in plasma samples obtained from 27 patients at baseline (pre-treatment) and at weekly intervals during Val-boroPro treatment (pre-treatment sample from one patient was not obtained).…”

Section: Resultsmentioning

confidence: 99%

Phase II trial of single agent Val-boroPro (talabostat) inhibiting fibroblast activation protein in patients with metastatic colorectal cancer

Narra¹,

Mullins²,

Lee³

et al. 2007

Cancer Biology & Therapy

212

167

View full text Add to dashboard Cite

Purpose: Fibroblast Activation Protein (FAP) is a tumor fibroblast protease that has been shown to potentiate colorectal cancer growth. The clinical impact of FAP inhibition was tested using Val-boroPro (Talabostat), the first clinical inhibitor of FAP enzymatic activity, in a phase II study of patients with metastatic colorectal cancer.Methods: Patients with metastatic colorectal cancer who had previously received systemic chemotherapies were treated with single agent Val-boroPro 200 μg p.o. BID continuously. Eligibility included measurable disease, performance status of 0 to 2, and adequate organ function. Laboratory correlates evaluated the pharmacodynamic effects of Val-boroPro on FAP enzymatic function in the peripheral blood.Results: Twenty-eight patients (median age 62; 12 males, 16 females) were enrolled in this study. There were no objective responses. Six of 28 (21%) patients had stable disease for a median of 25 weeks (range 11-38 weeks). Laboratory analysis demonstrated significant, although incomplete inhibition of FAP enzymatic activity in the peripheral blood.Conclusion: This phase II trial of Val-boroPro demonstrated minimal clinical activity in patients with previously treated metastatic colorectal cancer. However it provides the initial proof-of-concept that physiologic inhibition of FAP activity can be accomplished in patients with colorectal cancer, and lays the groundwork for future studies targeting the tumor stroma.

show abstract

“…The homodimer is located in cellular vesicles that are distinct from lysosomes and secretion is regulated by an increased Ca 21 flux [77]. Using chromogenic substrates, DPP2 displays post-proline dipeptidyl aminopeptidase activity similar to DPP4, however, over a broad pH range with an acidic to neutral pH optimum [76,78,80]. While DPP2 hydrolyses tripeptides readily, its activity decreases rapidly with increasing chain length of peptide.…”

Section: Non-related Dpp4-like Enzymesmentioning

confidence: 99%

“…The soluble serine protease contains a proform and has a length of 492 amino acids with a molecular weight of 58 kDa [77,78]. Glycosylation and dimerization are required for the catalytic activity and the latter occurs via a leucine zipper motif, which is novel for proteases [79].…”

Section: Non-related Dpp4-like Enzymesmentioning

confidence: 99%

Unravelling the immunological roles of dipeptidyl peptidase 4 (DPP4) activity and/or structure homologue (DASH) proteins

Wagner¹,

Klemann²,

Stephan

et al. 2016

Clinical and Experimental Immunology

107

View full text Add to dashboard Cite

SummaryDipeptidyl peptidase (DPP) 4 (CD26, DPP4) is a multi-functional protein involved in T cell activation by co-stimulation via its association with adenosine deaminase (ADA), caveolin-1, CARMA-1, CD45, mannose-6-phosphate/insulin growth factor-II receptor (M6P/IGFII-R) and C-X-C motif receptor 4 (CXC-R4). The proline-specific dipeptidyl peptidase also modulates the bioactivity of several chemokines. However, a number of enzymes displaying either DPP4-like activities or representing structural homologues have been discovered in the past two decades and are referred to as DPP4 activity and/or structure homologue (DASH) proteins. Apart from DPP4, DASH proteins include fibroblast activation protein alpha (FAP), DPP8, DPP9, DPP4-like protein 1 (DPL1, DPP6, DPPX L, DPPX S), DPP4-like protein 2 (DPL2, DPP10) from the DPP4-gene family S9b and structurally unrelated enzyme DPP2, displaying DPP4-like activity. In contrast, DPP6 and DPP10 lack enzymatic DPP4-like activity. These DASH proteins play important roles in the immune system involving quiescence (DPP2), proliferation (DPP8/DPP9), antigen-presenting (DPP9), costimulation (DPP4), T cell activation (DPP4), signal transduction (DPP4, DPP8 and DPP9), differentiation (DPP4, DPP8) and tissue remodelling (DPP4, FAP). Thus, they are involved in many pathophysiological processes and have therefore been proposed for potential biomarkers or even drug targets in various cancers (DPP4 and FAP) and inflammatory diseases (DPP4, DPP8/DPP9). However, they also pose the challenge of drug selectivity concerning other DASH members for better efficacy and/or avoidance of unwanted side effects. Therefore, this review unravels the complex roles of DASH proteins in immunology.Keywords: antigen presentation/processing, CD26, co-stimulation, DPP4 activity and/or structure homologue proteins (DASH), signal transductionThe dipeptidyl peptidase (DPP)4 family of DPP4 activity and/or structure homologue (DASH) proteins Within the last two decades a number of enzymes have been discovered to also display DPP4-like activity or are structural homologues to DPP4. These enzymes/proteins are referred to as DPP4 activity and/or structure homologue (DASH) proteins, and can be grouped into the DPP4 gene family and non-related DPP4-like enzymes. Except for DPL1 and DPL2, all members display DPP4-like activity with neutral to basic pH optima and similar inhibition profiles [6,7]. DPP4 (CD26). DPP4 (CD26) is the best-known DASH protein and has been described in detail elsewhere [7][8][9].

show abstract

Dipeptidyl peptidase II (DPPII), a review

Cited by 68 publications

References 168 publications

Mice lacking asparaginyl endopeptidase develop disorders resembling hemophagocytic syndrome

Mice lacking asparaginyl endopeptidase develop disorders resembling hemophagocytic syndrome

Phase II trial of single agent Val-boroPro (talabostat) inhibiting fibroblast activation protein in patients with metastatic colorectal cancer

Unravelling the immunological roles of dipeptidyl peptidase 4 (DPP4) activity and/or structure homologue (DASH) proteins

Contact Info

Product

Resources

About