Ctsl Antibody
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Description
Mechanism of Action
CTSL antibodies function by binding to specific epitopes on the CTSL protein, thereby inhibiting its proteolytic activity. This disruption blocks CTSL’s ability to cleave target substrates, such as viral spike proteins, which are essential for viral entry into host cells. For example, studies demonstrate that CTSL cleaves the SARS-CoV-2 spike protein, facilitating viral fusion and infection . Antibody-mediated inhibition of CTSL has been shown to reduce pseudovirus infection in vitro by up to 76% .
2.1. Role in SARS-CoV-2 Infection
CTSL expression is elevated in COVID-19 patients and correlates with disease severity . Experimental data reveal that CTSL knockdown significantly reduces SARS-CoV-2 pseudovirus entry into host cells, while overexpression enhances infection . Amantadine, a licensed anti-influenza drug, has been identified as a CTSL inhibitor, demonstrating therapeutic potential .
2.2. Antibody Development
A humanized antibody fusion (Syn-LC-CTSLpp) has been engineered by fusing the inhibitory propeptide of procathepsin L to an antibody scaffold. This construct exhibits a K_i of 0.090 ± 0.015 nM for CTSL, with >100-fold specificity over related proteases like CTSS . The antibody’s binding affinity (K_D = 5.495 nM) and stability under physiological conditions make it a promising candidate for therapeutic applications .
2.3. Cancer Applications
High CTSL expression in lung and glioma tissues correlates with poor prognosis, suggesting its role in tumor progression . Antibodies targeting CTSL may inhibit cancer-associated proteolysis while reducing SARS-CoV-2 susceptibility in cancer patients .
3.1. Diagnostic Tools
Commercial antibodies like MAB9521 (R&D Systems) enable detection of CTSL in Western blots and IHC. This antibody shows no cross-reactivity with other cathepsins (e.g., CTSB, CTSS) and specifically binds CTSL at ~35 kDa .
3.2. Therapeutic Candidates
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Syn-LC-CTSLpp: A humanized antibody fusion with subnanomolar CTSL inhibition .
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Amantadine: A repurposed drug shown to inhibit CTSL activity post-infection .
Table 2: CTSL Inhibitors
Product Specs
Buffer
Preservative: 0.03% Proclin 300
Constituents: 50% Glycerol, 0.01M PBS, pH 7.4
Constituents: 50% Glycerol, 0.01M PBS, pH 7.4
Form
Liquid
Lead Time
Made-to-order (12-14 weeks)
Synonyms
Ctsl antibody; Ctsl1Cathepsin L1 antibody; EC 3.4.22.15 antibody; Cathepsin L antibody; Major excreted protein antibody; MEP antibody; p39 cysteine proteinase) [Cleaved into: Cathepsin L1 heavy chain; Cathepsin L1 light chain] antibody
Target Names
Uniprot No.
Target Background
Function
Cathepsin L is a thiol protease that plays a crucial role in the degradation of proteins within lysosomes. It is involved in various cellular processes, including:
- Solubilization of cross-linked thyroglobulin and subsequent release of thyroid hormone thyroxine (T4) through limited proteolysis in the thyroid follicle lumen.
- Processing of the prohormone proenkephalin into the active enkephalin peptide neurotransmitter in neuroendocrine chromaffin cells secretory vesicles.
- Regulation of CD4(+) T cell positive selection in the thymus by generating MHCII-bound peptide ligands presented by cortical thymic epithelial cells.
- Mediation of invariant chain processing in cortical thymic epithelial cells.
- Acting as a major elastin-degrading enzyme at neutral pH.
- Accumulation as a mature and active enzyme in the extracellular space of antigen presenting cells (APCs) to regulate extracellular matrix degradation during inflammation.
- Generation of endostatin from COL18A1 in its secreted form.
- Contribution to cardiac morphology and function.
- Playing a vital role in hair follicle morphogenesis and cycling, as well as epidermal differentiation.
- Enhancement of steroidogenesis stimulation by TIMP1.
Gene References Into Functions
- Research suggests that CTSL contributes to the proliferation and metastasis of breast cancer and could serve as a potential therapeutic target for breast cancer treatment. PMID: 26639231
- CTSL is causally involved in the pathogenesis of experimental diabetic nephropathy. PMID: 27575559
- Findings indicate that single chain-cathepsin L is biologically active in promoting Th17 generation and is counter-regulated by serpinB1 and asparagine endopeptidase. PMID: 26343333
- CTSL plays a significant role in MHC class II-mediated peptide presentation in thymic epithelial cells, participating in both invariant chain degradation and the generation of MHC class II-bound peptide ligands presented by cortical thymic epithelial cells. Consequently, CTSL is essential for the positive selection of CD4+ T cells in the thymus. PMID: 11119260
- Genetic inhibition of cathepsin L activity is inferred to retard Myc-driven tumor growth, suggesting the potential therapeutic value of pharmacological inhibitors of cysteine cathepsins in treating advanced tumors. PMID: 25927437
- The phenotypes of cathepsin L deficiency can be attributed solely to the lack of canonically targeted cathepsin L, while the biogenesis and functionality of nucleo-cytosolic cathepsin L remain unknown. PMID: 25222295
- In vivo functional evidence supports the role of overexpressed CTSL as a promoter of lung metastasis, with high CTSL levels being maintained during tumor progression due to stress-resistant mRNA translation. PMID: 25957406
- Cathepsin L has a protective function in mouse skin carcinogenesis. PMID: 21538579
- Cathepsin L is involved in nociception in mice, and peripheral autophagy and cathepsin L contribute to the antinociceptive effect of dimethoxybenzylidene in mice. PMID: 23912553
- A degradative Ctsl-MMP-2 axis is observed, resulting in increased MMP-2 levels upon cathepsin deficiency and subsequent degradation of secreted proteins such as collagen alpha-1 (I). PMID: 23811845
- Cathepsin L protects mice from mycoplasmal infection and is essential for airway lymphangiogenesis. PMID: 23600672
- B-cell lymphopoiesis is regulated by cathepsin L. PMID: 23585893
- Lysosomal CTSL attenuates cardiac hypertrophy and preserves cardiac function by facilitating autophagy and proteasomal protein processing. PMID: 23608608
- Two novel thyroiditogenic thyroglobulin (Tg) epitopes are located near cathepsin L cleavage sites, clustered close to known immunopathogenic Tg epitopes. PMID: 23315080
- Bushen tiaojing recipe and xiaoyao pill promote ovulation by enhancing the expression of CatL. PMID: 21434350
- Cathepsins L and Z play a critical role in degrading polyglutamine-containing proteins within lysosomes. PMID: 22451661
- Cathepsin L contributes to abdominal aortic aneurysms formation by promoting lesion inflammatory cell accumulation, angiogenesis, and protease expression. PMID: 21868704
- Cathepsin L deficiency affects, albeit to a limited extent, the abundance of extracellular matrix (ECM) components, signaling proteins, and other proteases as well as endogenous protease inhibitors. PMID: 21972973
- Defects in DNA repair associated with 53BP1 deficiency upon loss of A-type lamins are attributed to upregulation of CTSL. PMID: 21750527
- Cathepsin L deficiency significantly reduced lung granuloma number in a mouse model of sarcoidosis. PMID: 21251246
- CTSL regulates cardiac repair and remodeling following myocardial infarction through multiple pathways. PMID: 21147810
- Downregulation of cathepsin L prevents autoimmune diabetes by suppressing CD8(+) T cell activity. PMID: 20877570
- Studies using embryonic cells from Ctsl knockout mice confirm Ctsl as a major protease involved in the turnover of phagosomes/lysosomes. PMID: 20536383
- Granule-bound cathepsins are essential for processing perforin to its active form, and CatL is a significant participant in this process. PMID: 20497254
- Cathepsin L expressed in endothelial progenitor cells plays a critical role in intraocular angiogenesis. PMID: 20304958
- A tightly regulated balance between cathepsin L and cystatin M/E is essential for tissue integrity in the epidermis, hair follicles, and corneal epithelium. PMID: 20495178
- NOD knock-out mice exhibit complete resistance to diabetes. PMID: 19664906
- Data suggest that Ctsl is critical for the termination of growth factor signaling in the endosomal/lysosomal compartment of keratinocytes and, therefore, functions as an anti-tumor protease. PMID: 20023699
- In mouse models of pancreatitis, the absence of cathepsin L induces apoptosis and reduces disease severity. PMID: 19900452
- Results suggest that cathepsin L functions as a major protease responsible for CCK8 production in mouse brain cortex, and participates with PC1/3 for CCK8 production in pituitary cells. PMID: 19589362
- For a subset of antigens, epitope generation is critically regulated by cathepsin L, which participates in antigen processing and generates qualitative and quantitative differences in the peptide repertoires displayed by MHC class II molecules. PMID: 11884425
- An alternate targeting pathway for procathepsin L in mouse fibroblasts. PMID: 11929604
- Dilated cardiomyopathy in mice deficient for the lysosomal cysteine peptidase cathepsin L. PMID: 11972068
- Cathepsin L is the primary mediator of reovirus disassembly. PMID: 11986312
- Cathepsin L regulates CD4+ T cell selection independently of its effect on invariant chain, playing a role in the generation of positively selecting peptide ligands. PMID: 12021314
- Mice lacking cathepsin L exhibit neuronal loss and brain atrophy, highlighting its crucial role in maintaining the central nervous system. PMID: 12048238
- Cathepsin L demonstrates evolution in placental expression through gene duplication. PMID: 12054558
- Cathepsin L plays a critical role in hair follicle morphogenesis and cycling, as well as epidermal differentiation. PMID: 12163394
- Regulation of the phagosomal CatL, CatB, CatS and CatZ contents during dendritic cell activation. PMID: 12186844
- Studies of thymocytes from knockout mice demonstrate a specific role for catL in regulating the presentation of natural CD1d ligands mediating V(alpha)14(+)NK1.1(+) T cell selection. PMID: 12368909
- Major histocompatibility complex class II-associated invariant chain controls the activity of extracellular cathepsin L. PMID: 12417635
- Data indicate that impaired cathepsin-L function may lead to gingival overgrowth, as observed in patients treated with calcium antagonists. PMID: 12466121
- Cathepsin L prevents atrophy of seminiferous tubules and promotes the formation of preleptotene spermatocytes and their differentiation into pachytene spermatocytes. PMID: 12533435
- Cathepsin L plays a regulatory role in the early stages of mammary gland involution. PMID: 12815617
- Cathepsin L has a previously uncharacterized biological role in the production of [Met]enkephalin, an endogenous peptide neurotransmitter. PMID: 12869695
- Muscle cathepsin L gene expression is increased in diabetes-prone mice and is correlated with glucose tolerance. PMID: 12941783
- A cathepsin L isoform lacking a signal peptide localizes to the nucleus in S phase and processes the CDP/Cux transcription factor. PMID: 15099520
- Cathepsin L and alpha(3) integrin play roles in podocyte migration. PMID: 15197181
- Research suggests that cathepsin L plays a crucial role in the integration of circulating endothelial progenitor cells (EPC) into ischemic tissue and is required for EPC-mediated neovascularization. PMID: 15665831
Database Links
Protein Families
Peptidase C1 family
Subcellular Location
Lysosome. Apical cell membrane; Peripheral membrane protein; Extracellular side. Secreted, extracellular space. Secreted. Cytoplasmic vesicle, secretory vesicle, chromaffin granule.
Tissue Specificity
Expressed in thymus, kidney and liver. Expressed in thyroid epithelial cells. Expressed in cortical thymic epithelial cells. Expressed by antigen presenting cells (APCs) such as dendritic cells and macrophages.
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