ArticleImmunology2010
Human and mouse perforin are processed in part through cleavage by the lysosomal cysteine proteinase cathepsin L.
Article in Immunology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 52 citations in OpenAlex.
- CTSL loss leads to anti-PD-1 immunotherapy resistance in lung cancer by suppressing the anti-tumor function of peripheral CD8Frontiers in immunology · 2026Article
- Cathepsin L as a dual-target to mitigate muscle wasting while enhancing anti-tumor efficacy of anti-PD-L1.Nature communications · 2025Article
- Disrupting membranes, controlling cell fate: the role of pore-forming proteins in cell death and therapy.Apoptosis : an international journal on programmed cell death · 2025Review
- Ammonia Suppresses the Antitumor Activity of Natural Killer Cells and T Cells by Decreasing Mature Perforin.Cancer research · 2025Article
- Cathepsin S: molecular mechanisms in inflammatory and immunological processes.Frontiers in immunology · 2025Review
- The multifaceted roles of cathepsins in immune and inflammatory responses: implications for cancer therapy, autoimmune diseases, and infectious diseases.Biomarker research · 2024Review
- Modulation of lytic molecules restrain serial killing in γδ T lymphocytes.Nature communications · 2023Article
- Identification of immune infiltration-related biomarkers in carotid atherosclerotic plaques.Scientific reports · 2023Article
- Cysteine Cathepsins as Therapeutic Targets in Immune Regulation and Immune Disorders.Biomedicines · 2023Review
- Lysosomal peptidases-intriguing roles in cancer progression and neurodegeneration.FEBS open bio · 2022Review
- Helicobacter pylori and gastric cancer: a lysosomal protease perspective.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2022Review
- Spatial localization of cathepsins: Implications in immune activation and resolution during infections.Frontiers in immunology · 2022Review
- Locked and Loaded: Mechanisms Regulating Natural Killer Cell Lytic Granule Biogenesis and Release.Frontiers in immunology · 2022Review
- Cystatin F acts as a mediator of immune suppression in glioblastoma.Cellular oncology (Dordrecht, Netherlands) · 2021Article
- Human CD4+ T-Cell Clone Expansion Leads to the Expression of the Cysteine Peptidase Inhibitor Cystatin F.International journal of molecular sciences · 2021Article
- The Optimization and Biological Significance of a 29-Host-Immune-mRNA Panel for the Diagnosis of Acute Infections and Sepsis.Journal of personalized medicine · 2021Article
- The Role of Cysteine Peptidases in Hematopoietic Stem Cell Differentiation and Modulation of Immune System Function.Frontiers in immunology · 2021Review
- Extracellular Cystatin F Is Internalised by Cytotoxic T Lymphocytes and Decreases Their Cytotoxicity.Cancers · 2020Article
- Review
- Cysteine cathepsins L and X differentially modulate interactions between myeloid-derived suppressor cells and tumor cells.Cancer immunology, immunotherapy : CII · 2020Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The pore-forming protein perforin is synthesized as an inactive precursor in natural killer (NK) cells and cytotoxic T lymphocytes (CTLs), and becomes active when a short C-terminal peptide is cleaved within acidic lysosome-like cytotoxic granules. Although it was shown more than a decade ago that this cleavage is pH dependent and can be inhibited by the generic cysteine cathepsin inhibitor E-64d, no protease capable of processing the perforin C terminus has been identified. Neither is it known whether a single protease is responsible or the processing has inbuilt redundancy. Here, we show that incubation of human NK cells and primary antigen-restricted mouse CTLs with the cathepsin L (CatL) inhibitor L1 resulted in a marked inhibition of perforin-dependent target cell death and reduced perforin processing. In vitro, CatL preferentially cleaved a site on full-length recombinant perforin close to its C terminus. The NK cells of mice deficient in CatL showed a reduction but not a complete absence of processed perforin, indicating that cysteine proteases other than CatL are also able to process perforin. We conclude that 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.
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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.