Disease relevance of Ctsl

• In addition, reduced cathepsin-L activity may play an important role in inducing drug-induced gingival overgrowth [1].
• Here, we show that the induction of puromycin aminonucleoside nephrosis involves podocyte migration conducted by a coordinated interplay between the cysteine protease cathepsin L and alpha(3) integrin [2].
• Since cathepsin-L deficiency was reported to be associated with thickening of the skin, impaired cathepsin-L activity may play a key role in the establishment of skin and gingival abnormalities seen in I-cell disease [1].
• Podocyte migration during nephrotic syndrome requires a coordinated interplay between cathepsin L and alpha3 integrin [2].
• Cathepsin L and/or K participate in bone resorption based on bone type-1 collagen degradation and the L-type protease inhibitors suppressed the bone resorption [3].

High impact information on Ctsl

• Notably, the protease cathepsin L (CathL) was highly expressed in EPC as opposed to endothelial cells and was essential for matrix degradation and invasion by EPC in vitro [4].
• Cathepsin L was found to be necessary for Ii degradation in cortical thymic epithelial cells (cTECs), but not in bone marrow (BM)-derived antigen-presenting cells (APCs) [5].
• Cathepsin L: critical role in Ii degradation and CD4 T cell selection in the thymus [5].
• We show that mice lacking the endosomal protease cathepsin L (catL) have greatly reduced numbers of V(alpha)14(+)NK1.1(+) T cells [6].
• A cathepsin L isoform that is devoid of a signal peptide localizes to the nucleus in S phase and processes the CDP/Cux transcription factor [7].

Chemical compound and disease context of Ctsl

• In contrast, Moloney murine sarcoma virus-transformed BALB/3T3 fibroblasts (MMSV) secreted greatly increased amounts of latent cathepsin B (17-fold) and latent cathepsin L (27-fold), and moderately increased amounts of active beta-glucuronidase (2-fold) in a manner which was not further increased by monensin [8].
• At the same time, a marked increase in cathepsin B and cathepsin L activity in LS lymphosarcoma was found, indicating the involvement of apoptosis in the mechanism of antitumor action of cyclophosphamide [9].
• Development of metastases was not associated with changes in cathepsin B activity in the liver, while activity of cathepsin L decreased only during the early period (4 days) after injection of gadolinium chloride [10].
• We found that only 5 min of incubation at 37 degrees C were required for nearly 100% of B. burgdorferi to enter a lysosomal glycoprotein-positive compartment, whereas 60 min were required for 90% of the spirochetes to appear in a cathepsin L-positive compartment under the same conditions [11].
• CpG dinucleotides, not methylated in any melanoma cells analysed, were methylated in a B lymphoma cell line, which poorly express cathepsin L. Our data demonstrate that in lymphoma cells, cathepsin L silencing was methylation-dependent [12].

Biological context of Ctsl

• Progesterone-regulated genes in the ovulation process: ADAMTS-1 and cathepsin L proteases [13].
• The expression and function of cystatin C and cathepsin B and cathepsin L during mouse embryo implantation and placentation [14].
• Asparagine endopeptidase is not essential for class II MHC antigen presentation but is required for processing of cathepsin L in mice [15].
• Also cathepsin L participates in cell apoptosis mediated by caspase III activation [3].
• Mature cathepsin L showed the same relative order of substrate specificity as its proenzyme form, but the absolute rates were about 5-fold greater [16].

Anatomical context of Ctsl

• These results demonstrate that a mutation in the Ctsl gene influences the levels of ECM components in lymphoid organs, the thymic output, and the number of T cells in the periphery [17].
• Both cathepsin B message and cathepsin L protein were localized to the mature, invasive trophoblast giant cells [14].
• To examine this issue, we generated embryonic fibroblast lines that express CL, CS, or neither [18].
• Cathepsin L expression and activity were induced in podocytes lacking alpha(3) integrin [2].
• Consistent with this finding, expression of cathepsin L was detected in the giant trophoblast cells of the ectoplacental cone on day 7 of pregnancy [19].

Associations of Ctsl with chemical compounds

• A protein affinity strategy employing recombinant CTLA-2beta helped us to determine that cathepsin L, a cysteine protease, is one of its targets in the pregnant uterus [19].
• In summary, these data establish that podocyte foot process effacement is a migratory event involving a novel interplay between cathepsin L and alpha(3) integrin [2].
• Isolated podocytes from mice lacking cathepsin L are protected from cell puromycin aminonucleoside-induced cell detachment [2].
• The selective suppression of cathepsin-L activity appeared not to be dependent on Ca(2+), since treatment of the cells with thapsigargin suppressed both cathepsin-B and -L activity [1].
• A calcium antagonist, nifedipine, specifically suppressed cathepsin-L activity and mRNA expression, but not that of cathepsin-B in cultured gingival fibroblasts [1].

Regulatory relationships of Ctsl

• Cathepsin S regulates the expression of cathepsin L and the turnover of gamma-interferon-inducible lysosomal thiol reductase in B lymphocytes [20].
• Thus, we propose a novel role for cathepsin L in regulating positive selection by generating the major histocompatibility complex class II bound peptide ligands presented by cortical thymic epithelial cells [21].
• Cathepsin-L influences the expression of extracellular matrix in lymphoid organs and plays a role in the regulation of thymic output and of peripheral T cell number [17].

Other interactions of Ctsl

• We conclude that AEP is essential for processing of Cat L but not for class II MHC-restricted Ag presentation [15].
• Synthesis and secretion of CAL were up-regulated by 1alpha,25-(OH)2D3, but neither those of CAK, dominant relative to CAL, nor CAB, barely detectable, levels changed in the experiments [22].
• These results show that neither cathepsin L nor S is required for activation of DPPI and suggest that one or more additional proteases is responsible [23].
• Active cathepsin L was highest at Day 9.5 in visceral yolk sac, a stage at which it has been shown that proteolysis in this organ is required for production of amino acids for embryonic protein synthesis [24].
• RESULTS: Expression of mRNAs for receptors of the growth factors, the proteinases and their inhibitors were confirmed. bFGF increased the secretion of cathepsin L (5.04-fold at 20 ng/mL), but did not alter the secretion of its extracellular inhibitor, cystatin C [25].

Analytical, diagnostic and therapeutic context of Ctsl

• The activity of cathepsin-L was suppressed up to 50% at 24 hours after treatment of the cells with the reagent [1].
• It is immunoprecipitated by anti-(cathepsin L) antibodies, and appears as the 25 kDa band of mature cathepsin L in Western blots [26].
• Furthermore, catalytically active cathepsin L was localized to the nucleus during the G1-S transition as detected by immunofluorescence imaging and labeling using activity-based probes [7].
• By electron microscopy, CTSL-deficient cardiomyocytes contained multiple large and apparently fused lysosomes characterized by storage of electron-dense heterogeneous material [27].
• Cellular studies showed the colocalization of cathepsin L with [Met]enkephalin in secretory vesicles of neuroendocrine chromaffin cells by immunofluorescent confocal and immunoelectron microscopy [28].

References