Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01034 (cystatin C)
 3,397 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The lysosomal cysteine proteinase cathepsin B is shown to be secreted by ten human colon carcinoma cell lines and to accumulate in culture media as a latent enzyme. The cell lines also secrete a physiological inhibitor of cathepsin B, cystatin C. A significant correlation was found between secretion of the latent enzyme and the inhibitor (r = 0.755, P < 0.01). The aim of the present study was to modulate the respective secretion of the two antagonists to test whether or not latency of cathepsin B was due to the concomitant secretion of the inhibitor. SW480 colon carcinoma cells were treated with the acidotropic agent ammonium chloride, phorbol 12-myristate 13-acetate, and the inflammatory cytokines TGF-beta, TNF-alpha, and IL-1 beta. Ammonium chloride significantly increased latent cathepsin B levels without affecting the constitutive secretion of cystatin C. Phorbol 12-myristate 13-acetate induced a 4- to 5-fold increase in secreted latent cathepsin B, but did not alter significantly the accumulation of cystatin C in media. The cytokines, TGF-beta, TNF-alpha, and IL-1 beta, had no major effect on the expression of these two antagonists. Latent cathepsin B released from human carcinoma cells could be efficiently activated by neutrophil elastase at neutral pH. It is concluded that latent cathepsin B is a true proenzyme rather than an enzyme-inhibitor complex. In addition, our data from neutrophil elastase activation experiments indicate that a proteolytic system for activation of the tumor cell-secreted latent enzyme may exist in vivo.
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PMID:Latency of cathepsin B secreted by human colon carcinoma cells is not linked to secretion of cystatin C and is relieved by neutrophil elastase. 820 57

Lysozyme is a major component of airway epithelial secretions, acts as cationic anti-microbial protein for innate immunity. Although lysozyme plays an important role in airway defense and is a key component of airway secretions under inflammatory conditions, little is understood about the regulation of its expression and the associated signaling pathway. We wanted to examine whether Phorbol 12-myristate 13-acetate (PMA), one of PKC activators, treatment of the airway epithelial cell line NCI-H292 increases lysozyme gene expression. In this study, we sought to determine which signal molecules are involved in PMA-induced lysozyme gene expression. We found that PKC and mitogen-activating protein/ERK2 kinase are essential for PMA-induced lysozyme expression and also mediate the PMA-induced activation of c-Myb protein. We identified a proximal region of the lysozyme promoter essential for promoter activity containing c-Myb transcription factor binding site. Additionally, by site-directed promoter mutagenesis, we identified that c-Myb preferred the CAA motif of the -85/-73 region of the lysozyme promoter. Finally, we showed that overexpression of c-Myb without PMA treatment increased the lysozyme promoter activity and protein expression. From these results, we conclude that PMA induces overexpression of lysozyme via ERK1/2 MAP kinase-c-Myb signaling pathways in NCI-H292 cells.
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PMID:Activation of c-Myb transcription factor is critical for PMA-induced lysozyme expression in airway epithelial cells. 2052 9