ArticleThe Journal of biological chemistry2010
Cathepsin H is an additional convertase of pro-granzyme B.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 74 citations in OpenAlex.
- CTSH regulates β-cell function and disease progression in newly diagnosed type 1 diabetes patients.Proceedings of the National Academy of Sciences of the United States of America · 2014Trial
- Review
- Granzyme B and melittin in cancer immunotherapy: molecular mechanisms and therapeutic perspectives in head and neck cancers.Frontiers in immunology · 2025Review
- Unraveling the phenotypic states of human innate-like T cells: Comparative insights with conventional T cells and mouse models.Cell reports · 2024Article
- Quantitative Proteomic Analysis Reveals Functional Alterations of the Peripheral Immune System in Colorectal Cancer.Molecular & cellular proteomics : MCP · 2024Article
- Immune Regulation and Immune Therapy in Melanoma: Review with Emphasis on CD155 Signalling.Cancers · 2024Review
- Pharmacologic inhibition of dipeptidyl peptidase 1 (cathepsin C) does not blockFrontiers in pharmacology · 2024Article
- Assessment of serum granulysin and cathepsin-L levels in vitiligo patients.Revista da Associacao Medica Brasileira (1992) · 2024Article
- Unraveling the Phenotypic States of Human innate-like T Cells: Comparative Insights with Conventional T Cells and Mouse Models.bioRxiv : the preprint server for biology · 2023Article
- Cathepsin H Knockdown Reverses Radioresistance of Hepatocellular Carcinoma via Metabolic Switch Followed by Apoptosis.International journal of molecular sciences · 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
- Locked and Loaded: Mechanisms Regulating Natural Killer Cell Lytic Granule Biogenesis and Release.Frontiers in immunology · 2022Review
- All About (NK Cell-Mediated) Death in Two Acts and an Unexpected Encore: Initiation, Execution and Activation of Adaptive Immunity.Frontiers in immunology · 2022Review
- Article
- Human CD4+ T-Cell Clone Expansion Leads to the Expression of the Cysteine Peptidase Inhibitor Cystatin F.International journal of molecular sciences · 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
- Lysosomal peptidases in innate immune cells: implications for cancer immunity.Cancer immunology, immunotherapy : CII · 2020Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The serine protease granzyme B (GrB) is the most potent proapoptotic cytotoxin of the granule exocytosis pathway of cytotoxic lymphocytes. GrB is synthesized as a zymogen (proGrB) and activated in cytotoxic granules by the lysosomal cysteine protease cathepsin C (CatC) which removes the N-terminal dipeptide Gly-Glu. It has been shown recently that mice lacking CatC nonetheless express significant residual GrB activity, indicating the presence of additional proGrB convertases. Here, we describe an assay to assess activation of proGrB and show that the amino-peptidase cathepsin H (CatH) has proGrB convertase activity in vitro, whereas dipeptidylpeptidase II does not. We generated mice lacking both CatC and CatH expression (CatCH(-/-)) and found that their lymphocytes have reduced convertase activity compared with those from CatC-deficient mice. Despite this, cytotoxic lymphocytes from CatCH(-/-) mice retain cytotoxic activity and some residual GrB activity. We conclude that CatH can act as an additional proGrB convertase and that other protease/s (apart from dipeptidylpeptidase II) must also possess convertase activity. This indicates a great deal of functional redundancy in GrB maturation, which would prevent pathogen-mediated immune suppression by via convertase inhibition.
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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.