ArticleThe Journal of biological chemistry2008
Cathepsin L is responsible for processing and activation of proheparanase through multiple cleavages of a linker segment.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.
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Who cites it
92 citing papers in PubMed, 175 citations in OpenAlex.
- Cathepsin L as a Driver of Tumour Invasion and a Novel Therapeutic Target in Ovarian Cancer.Cancers · 2026Review
- Self-assembling protein nanoparticles for cytosolic delivery of nucleic acids and proteins.Nature biotechnology · 2026Article
- Heparan Sulfate Proteoglycans (HSPGs) and Their Degradation in Health and Disease.Biomolecules · 2025Review
- Cathepsins: Emerging targets in the tumor ecosystem to overcome cancers.Seminars in cancer biology · 2025Review
- Endothelial eNOS deficiency causes podocyte injury through NFAT2 and heparanase in diabetic mice.Scientific reports · 2024Article
- Involvement of heparanase in the pathogenesis of acute pancreatitis: Implication of novel therapeutic approaches.Journal of cellular and molecular medicine · 2024Article
- The Uptake of Heparanase into Mast Cells Is Regulated by Its Enzymatic Activity to Degrade Heparan Sulfate.International journal of molecular sciences · 2024Article
- Review
- Article
- Heparanase-A single protein with multiple enzymatic and nonenzymatic functions.Proteoglycan research · 2023Review
- The Interplay of Glycosaminoglycans and Cysteine Cathepsins in Mucopolysaccharidosis.Biomedicines · 2023Review
- Flow-Induced Secretion of Endothelial Heparanase Regulates Cardiac Lipoprotein Lipase and Changes Following Diabetes.Journal of the American Heart Association · 2022Article
- Review
- Importance of Heparan Sulfate Proteoglycans in Pancreatic Islets and β-Cells.International journal of molecular sciences · 2022Review
- The Key Role of Lysosomal Protease Cathepsins in Viral Infections.International journal of molecular sciences · 2022Review
- Knockdown of CD44 inhibits proliferation, migration and invasion of osteosarcoma cells accompanied by downregulation of cathepsin S.Journal of orthopaedic surgery and research · 2022Article
- The Heparanase Regulatory Network in Health and Disease.International journal of molecular sciences · 2021Review
- A Marine λ-Oligocarrageenan Inhibits Migratory and Invasive Ability of MDA-MB-231 Human Breast Cancer Cells through Actions on Heparanase Metabolism and MMP-14/MMP-2 Axis.Marine drugs · 2021Article
- Heparanase expression and activity are increased in platelets during clinical sepsis.Journal of thrombosis and haemostasis : JTH · 2021Article
- Dual-Mechanism Quenched Fluorogenic Probe Provides Selective and Rapid Detection of Cathepsin L Activity*.ChemMedChem · 2021Article
32 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Heparanase is an endo-beta-d-glucuronidase that degrades heparan sulfate in the extracellular matrix and on the cell surface. Human proheparanase is produced as a latent protein of 543 amino acids whose activation involves excision of an internal linker segment (Ser(110)-Gln(157)), yielding the active heterodimer composed of 8- and 50-kDa subunits. Applying cathepsin L knock-out tissues and cultured fibroblasts, as well as cathepsin L gene silencing and overexpression strategies, we demonstrate, for the first time, that removal of the linker peptide and conversion of proheparanase into its active 8 + 50-kDa form is brought about predominantly by cathepsin L. Excision of a 10-amino acid peptide located at the C terminus of the linker segment between two functional cathepsin L cleavage sites (Y156Q and Y146Q) was critical for activation of proheparanase. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry demonstrates that the entire linker segment is susceptible to multiple endocleavages by cathepsin L, generating small peptides. Mass spectrometry demonstrated further that an active 8-kDa subunit can be generated by several alternative adjacent endocleavages, yielding the precise 8-kDa subunit and/or slightly elongated forms. Altogether, the mode of action presented here demonstrates that processing and activation of proheparanase can be brought about solely by cathepsin L. The critical involvement of cathepsin L in proheparanase processing and activation offers new strategies for inhibiting the prometastatic, proangiogenic, and proinflammatory activities of heparanase.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.