Human Dipeptidyl-peptidase I

Rao, Narayanam V.; Rao, Gopna V.; Hoidal, John R.

doi:10.1074/jbc.272.15.10260

Cited by 146 publications

(45 citation statements)

References 49 publications

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“…Also induced in both tissues were two genes involved in lysosomal proteolysis, cathepsin L and tubulointerstitial nephritis antigen-like precursor. In gill only, another lysosomal protease, dipeptidyl peptidase I precursor (Rao et al, 1997) was also induced. In addition, calpain 9, an intracellular, non-lysosomal cysteine protease with a broad suite of targets, was induced in both tissues.…”

Section: Cluster 4: Proteolysismentioning

confidence: 99%

The cellular response to heat stress in the gobyGillichthys mirabilis: a cDNA microarray and protein-level analysis

Buckley

Gracey

Somero

2006

Journal of Experimental Biology

239

221

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SUMMARY The cellular response to stress relies on the rapid induction of genes encoding proteins involved in preventing and repairing macromolecular damage incurred as a consequence of environmental insult. To increase our understanding of the scope of this response, a cDNA microarray, consisting of 9207 cDNA clones, was used to monitor gene expression changes in the gill and white muscle tissues of a eurythermic fish, Gillichthys mirabilis(Gobiidae) exposed to ecologically relevant heat stress. In each tissue, the induction or repression of over 200 genes was observed. These genes are associated with numerous biological processes, including the maintenance of protein homeostasis, cell cycle control, cytoskeletal reorganization,metabolic regulation and signal transduction, among many others. In both tissues, the molecular chaperones, certain transcription factors and a set of additional genes with various functions were induced in a similar manner;however, the majority of genes displayed tissue-specific responses. In gill,thermal stress induced the expression of the major structural components of the cytoskeleton, whereas these same genes did not respond to heat in muscle. In muscle, many genes involved in promoting cell growth and proliferation were repressed, perhaps to conserve energy for repair and replacement of damaged macromolecules, but a similar repression was not observed in the gill. Many of the observed changes in gene expression were similar to those described in model species whereas many others were unexpected. Measurements of the concentrations of the protein products of selected genes revealed that in each case an induction in mRNA synthesis correlated with an increase in protein production, though the timing and magnitude of the increase in protein was not consistently predicted by mRNA concentration, an important consideration in assessing the condition of the stressed cell using transcriptomic analysis.

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Section: Cluster 4: Proteolysismentioning

confidence: 99%

The cellular response to heat stress in the gobyGillichthys mirabilis: a cDNA microarray and protein-level analysis

Buckley

Gracey

Somero

2006

Journal of Experimental Biology

239

221

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“…Cathepsin C (CG) 3 is implicated in processing of certain lysosomal cathepsins (9) and in the degradation of intracellular proteins (7,10,11). More recently, cathepsin C was shown to activate several chymotrypsin-like serine proteases by removing an inhibitory N-terminal dipeptide.…”

mentioning

confidence: 99%

“…Cathepsin C (also known as dipeptidyl peptidase-1, EC 3.4.14.1) is a cysteine dipeptidyl aminopeptidase expressed in the lysosomes of several tissues, with levels highest in lung, macrophages, neutrophils, CD8ϩ T cells, and mast cells (1)(2)(3)(4)(5). The enzyme cleaves two-residue units from the N termini of proteins until it reaches a stop sequence, typically an arginine or lysine in P2 (6), a proline residue in P1 or P1Ј (7), or an isoleucine residue in P1 (8).…”

mentioning

confidence: 99%

Inhibition of the Activation of Multiple Serine Proteases with a Cathepsin C Inhibitor Requires Sustained Exposure to Prevent Pro-enzyme Processing

Méthot

Rubin

Guay

et al. 2007

Journal of Biological Chemistry

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Cathepsin C is a cysteine protease required for the activation of several pro-inflammatory serine proteases and, as such, is of interest as a therapeutic target. In cathepsin C-deficient mice and humans, the N-terminal processing and activation of neutrophil elastase, cathepsin G, and proteinase-3 is abolished and is accompanied by a reduction of protein levels. Pharmacologically, the consequence of cathepsin C inhibition on the activation of these serine proteases has not been described, due to the lack of stable and non-toxic inhibitors and the absence of appropriate experimental cell systems. Using novel reversible peptide nitrile inhibitors of cathepsin C, and cell-based assays with U937 and EcoM-G cells, we determined the effects of pharmacological inhibition of cathepsin C on serine protease activity. We show that indirect and complete inhibition of neutrophil elastase, cathepsin G, and proteinase-3 is achievable in intact cells with selective and non-cytotoxic cathepsin C inhibitors, at concentrations ϳ10-fold higher than those required to inhibit purified cathepsin C. The concentration of inhibitor needed to block processing of these three serine proteases was similar, regardless of the cell system used. Importantly, cathepsin C inhibition must be sustained to maintain serine protease inhibition, because removal of the reversible inhibitors resulted in the activation of pro-enzymes in intact cells. These findings demonstrate that near complete inhibition of multiple serine proteases can be achieved with cathepsin C inhibitors and that cathepsin C inhibition represents a viable but challenging approach for the treatment of neutrophil-based inflammatory diseases.

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“…The cathepsin C gene is expressed in epithelial regions commonly affected by Papillon lefevre syndrome such as palms, soles, knees and keratinized oral gingiva 16, 21 . The pathological clinical findings associated with Papillon lefevre syndrome suggest that cathepsin C is functionally important in structural growth and development of skin in susceptibility to periodontal disease 19 . It is unknown if the profound periodontal disease susceptibility is a consequence of altered integrity of junctional epithelium is eliminated, the severe gingival inflammation resolve s10 .…”

Section: 15mentioning

confidence: 99%