Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
The Database for Annotation, Visualization and Integrated Discovery
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DAVID Functional Annotation Table
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cathepsin L(CTSL) cathepsin L(CTSL) Related Genes Homo sapiens
CHROMOSOME 9,
CYTOBAND 9q21-q22,
ENSEMBL_GENE_ID ENSG00000135047,
ENTREZ_GENE_ID 1514,
GENERIF_SUMMARY cis-acting element on cathepsin L mRNA can be bound by a negative trans-acting regulator, thus leading to reduced expression rates, its activity resulted in extensive bone destruction in both cholesteatomas and noncholesteatomas of the middle ear, Characterization and comparative mapping of the porcine CTSL gene indicates a novel synteny between HSA9q21-->q22 and SSC10q11-->q12, the subcellular distribution of cathepsin B, L, and S ativities underwent a shift from endosome to lysosome localization during monocyte differentiation in cell culture, suppression of cathepsin L expression in A549 cells leads to a growth inhibition which is partially compensated by an upregulation of IL-8 production., cathepsin K and L processed high-molecular weight kininogen under stoichiometric conditions, only cathepsin L generated significant amounts of immunoreactive kinins. Cathepsin L exhibited higher specificity constants (kcat/Km) than tissue kallikrein, lack of involvement in degrading MHC class II-associated invariant chain in nonprofessional antigen-presenting cells, These results show that cathepsin L is secreted from human fibroblasts in response to external stimuli and plays an important role in IL-8 processing in inflammatory sites., The expression of cathepsin L in non-small cell lung cancer is not related to the patients' outcome at a statistically significant level., insulin-stimulated cathepsin L expression in skeletal muscle is impaired in diabetic but not in nondiabetic monozygotic twins, suggesting that the changes may be secondary to impaired glucose metabolism., Cathepsin L is released and catalytically active in T lymphocyte cytosol during supraoptimal activation-induced apoptosis of T cells in vitro and may participate in high dose tolerance in vivo., endothelial cell-associated cathepsins B and L are not involved in the invasive growth of capillaries from existing blood vessels and the presence of collagen is necessary for MMP2 expression in endothelial cells, The function of cathepsin L (catL) in the proteolytic network of human lung epithelial cells and its role in the regulation of apoptosis., serum level of cathepsin L can serve as a marker of bone resorption and bone density, Peptide fragment of p47 SEP is a reversible competitive inhibitor of cathepsin L., Mechanical stress (compression and tension forces) causes an increase in secretion of cathepsins B and L in periodontal ligament cells in vitro., Data suggest that cathepsin L has a critical role in the integration of circulating endothelial progenitor cells (EPC) into ischemic tissue and is required for EPC-mediated neovascularization., cathepsins B and L have roles in atypical pituitary adenoma, cathepsin and inhibitor expression was not different between central and peripheral meningioma tissue or between histological subtypes of meningiomas with the exception of cathepsin L, the level of which was significantly lower in transitional meningiomas, cathepsin L is over-expressed in human AAA and atherosclerotic lesions and its expression in vascular cell types found in these lesions is regulated by pro-inflammatory cytokines., The presence of active cathepsins L, K and S suggests that they contribute to the extracellular breakdown of the extracellular matrix., highest expression of Cat L was found in psoriasis, atopic eczema and squamous cell carcinoma, Identification of CTSV & CTSL as targets for cystatin M/E, their (co)-expression in the stratum granulosum of skin, and activity of CTSL toward transglutaminase 3 strongly imply an important role for them in the differentiation process of human epidermis., Results showed that the breast cancer cell line exhibiting the highest in vitro invasiveness also expressed the highest amount of cathepsin L splice variant L-A3., CTSL is expressed in the brain of these compound mutants, predominantly in neurons of the cerebral cortex and in Purkinje cells of the cerebellum, where it appears to prevent neuronal cell death, the 32-kDa cathepsin L found in HT 1080 cell medium is involved in cancer invasion and metastasis, analysis of human cathepsins K, L, and S iunteractions with elastins, level of active cathepsin B and L is increased in tumors, Results describe the structure of chagasin in complex with the host cysteine protease, cathepsin L, at 1.75 A resolution., over-expression of VEGF in human glioblastoma cells induces cathepsin L expression at the transcriptional level. This mechanism could be involved in the enhanced tumorogenic potential of these cells., Results describe the participation of cathepsin L in adipogenesis and glucose intolerance., Here we demonstrate a role for cathepsin L (CatL) cleavage of Ebola virus GP in the generation of a stable 18-kDa GP1 viral intermediate that exhibits increased binding to and infectivity for susceptible cell targets., did not detect any plasminogen degradation by cathepsins B, K and L., shortening the heavy-light chain loop does not change substrate affinity but does influence activity, in part via conformational change, These results indicated that in vivo a tumour hypoxic environment up-regulates cathepsin L expression which promotes tumour progression., Cathepsin L has a role in processing and activation of proheparanase through multiple cleavages of a linker segment, cathepsin L is involved in death of macrophages, necrotic core formation and development of atherosclerotic plaque instability, blood levels are significantly elevated in patients with colorectal adenoma and colorectal carcinoma, Cathepsin L is required for invasion of endothelial progenitor cells (EPC) into ischemic tissue; thereby its reduction may limit the functional capacity of EPC to improve neovascularization in diabetics., Caspase-3 activation triggers extracellular cathepsin L release and endorepellin proteolysis., These findings suggest that 229E takes an endosomal pathway for cell entry and that proteases like CPL are involved in this mode of entry., Cathepsin L and transglutaminase 3 could be involved in the pathway that leads to terminal differentiation, not only in the epidermis but also in the human hair follicle and nail unit., Study indicates that CTSL improves cardiac function and inhibits cardiac hypertrophy, inflammation, and fibrosis through blocking Akt/GSK3beta signaling., Serum Cathepsin L levels were significantly higher in coronary heart disease than in controls., High nuclear cathepsin L expression is associated with colorectal cancer., Cathepsin L is a potential biomarker for prognosis of nasopharyngeal carcinoma, unknown mRNA clone PP1959 identified as splice variant of cathepsin L mRNA which encodes truncated form of cathepsin L containing only 151 C-terminal amino acids; localization to nuclear, perinuclear & cytosolic region, Levels of CatB and CysC were higher in CF of malignant serous tumors compared to those found in benign serous tumors whereas levels of CatL were significantly higher in CF of malignant mucinous tumors compared to those found in benign mucinous tumors, Proteinuria can result from enzymatic cleavage of essential regulators of podocyte actin dynamics by cytosolic cathepsin L, resulting in a motile podocyte phenotype., The combination of cathepsin L inhibition with conventional chemotherapy seems to be more promising and has yielded more consistent results., Data show that SCCA-1 inhibition of cathepsin L-like proteolytic activity secreted from breast and melanoma cancer cell lines was significantly enhanced by heparin., Stefin B interacts with histones and cathepsin L in the nucleus, arsenite toxicity involves a complex interplay between autophagy and apoptosis in human glioblastoma cells and is associated with inhibition of Cathepsin B, and that this toxicity is highly exacerbated by simultaneous Cathepsin L inhibition., functions of CTSL and CTSV in the positive selection of CD4+ T cells, Granule-bound cathepsins are essential for processing perforin to its active form, and that CatL is an important, but not exclusive, participant in this process., analysis of CTSL1 gene transcript demonstrated that cathepsin L protein and transcript correlate both in fibroblasts expressing Ras mutants and in pharmacologically treated cells, thus indicating a transcriptional up-regulation, Results suggest a potential utility of CTSL and CTSB as prognostic markers for this malignancy., imbalance between catL and cystatin C in patients with coronary artery ectasia, These data indicate that cathepsins B, L and S may act as cell-death mediators in in monocytic cells infected with ICP4 and Us3 deletion mutant herpes simplex virus type 1., Plasma cathepsin L and placenta growth factor, acting as important modulators of angiogenesis, could be used as biomarkers to predict coronary collateral formation in patients with coronary heart disease., CTSL might increase the invasion and metastasis ability of ovarian cancer cells in vitro., abnormal distribution of cathepsin L may be responsible for dopamine neuron death, involved in the pathogenic cascade event for the development of Parkinson's disease., This study showed that cathepsin L provides significant prognostic information and that it might be a useful therapeutic target in the future., Studies indicate that cathepsin L as the heparanase activating protease., Data suggest that differential stability and translation initiation modes mediated by the 5'UTRs of human cathepsin L variants are involved in regulating its expression., Cathepsin L is present in the nucleus and regulates the transcription of effector caspases 3 and 7, in a p53 dependent manner., this is the first report demonstrating the phase-specific expression of CTSL in chronic myeloid leukaemia, Procathepsin L secretion, which triggers tumour progression, is regulated by Rab4a in human melanoma cells, CTSL1 is a target gene of the BACH1 transcription factor according to ChIP-seq analysis in HEK 293 cells., CTSL and CTSB are capable of directly processing both alpha- and beta-protryptases from human mast cells to their mature enzymatically active products., The cathepsin L deserves further evaluation as therapeutic targets to develop disease modifying drugs to treat Alzheimer's disease., Peroxisome proliferator-activated receptor gamma induces apoptosis and inhibits autophagy of human monocyte-derived macrophages via induction of cathepsin L, Cathepsin L- and K-cleaved chemerin trigger robust migration of human blood-derived plasmacytoid dendritic cells ex vivo, Processing of human protryptase in mast cells involves cathepsins L, B, and C., Overexpression of human CTSL in wild-type murine fibroblasts leads to decreased 53BP1 protein levels and changes in its cellular distribution, resulting in defective repair of DNA DSBs., Cathepsins K, L, and S activity are profiled in 10 mug human breast, lung, and cervical tumors., cathepsin L is highly expressed in GISTs compared to its expression in other cancerous lesions; this identifies cathepsin-L as a new diagnostic marker for GISTs., DHA supplementation significantly suppressed the expression of low-density lipoprotein receptor and cathepsin L1, both of which were also up-regulated by LPS., Data show that mRNA levels of the two main lysosomal enzymes (cathepsin B and L) were not changed but, conversely, genes related to calpain and caspase had a higher expression in the muscles of the patients., Cysteine cathepsins S and L modulate anti-angiogenic activities of human endostatin., high-resolution structures reveal that the backbone C=O group of Gly61 in most cathepsin L co-crystal structures maintains water solvation while engaging in halogen bonding, Recently discovered biological roles of cathepsins L and B indicate their significance in human health and disease., Elevated serum CL, Hpa, and MMP-9 levels are correlated with malignant invasion and progression in ovarian cancer., Cathepsin L has a strong preference for aromatic and, to a slightly lesser extent, aliphatic residues., Cathepsin L cleavage potentiates the Ebola virus GP to undergo a fusion-relevant conformational change., Cathepsins B and L activate Ebola but not Marburg virus glycoproteins for efficient entry into cell lines and macrophages independent of TMPRSS2 expression., Report transient expression of progesterone receptor and cathepsin-l in human granulosa cells during the periovulatory period., Regulation of cathepsins S and L by cystatin F during maturation of dendritic cells., Cathepsins L and Z are critical in degrading polyglutamine-containing proteins within lysosomes., Seminal plasma cathepsin B was approximately 70 times higher, while the cathepsin L values were approximately 500 times higher and the cathepsin S values approximately 40 times higher in seminal plasma than in a group of serum samples., Cathepsin L has a significant impact on antigen-induced arthritis severity by influencing the selection of Th cell populations in the thymus, but seems not play any significant role in the direct joint destruction, The activity of cathepsin B and L in blood significantly increased with age., conclude that common genetic variation in the proximal CTSL1 promoter, especially at position C-171A, is functional in cells, and alters transcription so as to explain the association of CTSL1 with BP in vivo, Cathepsin L expression is related to the invasive and metastatic potential of oral squamous cell carcinoma., In this study, various molecular dynamics (MD) simulations of pro- and mature human cathepsins L and O were performed., Up-regulation of cysteine cathepsins B and L and TGF-beta production/signaling were required for the activation of fibroblasts and their promotion of the invasive growth of melanoma cells., Oxidized low-density lipoprotein upregulated CATL protein levels and activation in human umbilical vein endothelial cells (ECs) in a concentration-dependent manner and stimulated EC autophagy and apoptosis and increased EC monolayer permeability., BRCA1 loss activates cathepsin L (CTSL)-mediated degradation of 53BP1., TMPRSS2 and HAT activate HCoV-229E for cathepsin L-independent virus-cell fusion., our data demonstrate that chronic UVA inhibits both cathepsin B and L enzymatic activity and that dual inactivation of both enzymes is a causative factor underlying UVA-induced impairment of lysosomal function in dermal fibroblasts., Thus, cathepsin L and cathepsin B are not required for human papillomavirus type 16 infection but instead appear to restrict infection., CTSL protein level was positively associated with forced expiratory volume in emphysema. The C allele of rs2274611 was associated with increased protein level. CTSL may be involved in the development of airflow limitation., Both cathepsin L and matrix metalloprotease-2 showed correlation with some of the clinicopathological parameters in pancreatic cancer but only cathepsin L expression in tumor epithelium predicted a poor prognosis for the disease., correlation of plasma CatL levels with aortic diameter and the lowest ankle-brachial index suggest that this cysteinyl protease plays a detrimental role in the pathogenesis of peripheral arterial diseases and abdominal aortic aneurysms, Data suggest that CTSL (cathepsin L) and CTSB (cathepsin B) of the autophagic-lysosomal proteolytic system are involved as the main proteolytic system in skeletal muscle during cancer cachexia development in patients with esophageal cancer., The increase in cathepsins B and L activities in lymphosarcoma tissues is caused by cyclophosphamide induction of apoptosis., Overexpression of CTSL is involved in tumor invasion and metastasis in ovarian cancer., catalase expression (or activity) was higher, while intracellular and extracellular Cat S, Cat L, and Cat K activities were lower in the non-invasive CL1-0 cells compared to the highly invasive CL1-5 cells., the results suggested that CTSL contributes to the proliferation and metastasis of OC, and that CTSL may be a novel molecular target for OC treatment., CTSL might involve in the development and progression of HCC as a oncogene., study showed plasma cathepsin L may be used as an independent predictor of prognosis in pancreatic cancer; this protease may be one of the factors responsible for tumor invasion, as its level was found to be significantly higher in pancreatic tumor tissues compared to non-neoplastic adjacent tissue, Cathepsins in Rotator Cuff Tendinopathy, The study determined almost identical substrate specificities for cysteine cathepsins K, L and S., TGFbetainduced epithelialmesenchymal transition was associated with increased cathepsin L in A549 and MCF7 cells. CATL may be involved in the regulation of EMT. CATL knockdown in A549 cells inhibited xenograft tumor growth and EMT in vivo, Cathepsins B and L activity correlates with the efficiency of reovirus-mediated tumor cell killing., in vivo functional evidence for overexpressed CTSL as a promoter of lung metastasis, whereas high CTSL levels are maintained during tumor progression due to stress-resistant mRNA translation., In addition, cathepsin L positively correlates with MMP2. PRACTICE, shedding of surface proteins by extracellular cathepsins impacts intracellular signaling as demonstrated for regulation of Ras GTPase activity., Cathepsin L targeting in cancer treatment, Knockdown of Cathepsin L promotes radiosensitivity of glioma stem cells both in vivo and in vitro., cathepsin L activity was decreased in p53 positive cells after adriamycin treatment, but not in p53 negative cells., these data indicate that the CTSL inhibitor KGP94 has the potential to alleviate metastatic disease progression and associated skeletal morbidities and hence may have utility in the treatment of advanced prostate cancer patients, Our findings highlight the potential role of CTSL in the cross talk between autophagy and apoptosis, which might be considered a therapeutic strategy for treatment of pathologic conditions associated with neurodegeneration., p41 fragment is also shown to reduce the secretion of interleukin-12 (IL-12/p70) during the subsequent maturation of treated dendritic cells.,
OFFICIAL_GENE_SYMBOL ctsl,
SP_COMMENT catalytic activity:Specificity close to that of papain. As compared to cathepsin B, cathepsin L exhibits higher activity toward protein substrates, but has little activity on Z-Arg-Arg-NHMec, and no peptidyl-dipeptidase activity., function:Important for the overall degradation of proteins in lysosomes., similarity:Belongs to the peptidase C1 family., subunit:Dimer of a heavy and a light chain linked by disulfide bonds.,