ArticleMolecular and cellular biology2005
Cationic sites on granzyme B contribute to cytotoxicity by promoting its uptake into target cells.
Article in Molecular and cellular biology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 84 citations in OpenAlex.
- Immunological synapse: structures, molecular mechanisms and therapeutic implications in disease.Signal transduction and targeted therapy · 2025Review
- Granzyme K activates the entire complement cascade.Nature · 2025Article
- Cell-associated galectin 9 interacts with cytotoxic T cells confers resistance to tumor killing in nasopharyngeal carcinoma through autophagy activation.Cellular & molecular immunology · 2025Article
- Modeling antibody drug conjugate potential using a granzyme B antibody fusion protein.BMC biology · 2024Article
- Improved Purification of Human Granzyme A/B and Granulysin Using a Mammalian Expression System.Frontiers in immunology · 2022Article
- Cytotoxic T cells are able to efficiently eliminate cancer cells by additive cytotoxicity.Nature communications · 2021Article
- Knocking 'em Dead: Pore-Forming Proteins in Immune Defense.Annual review of immunology · 2020Review
- Review
- Human Granzyme B Based Targeted Cytolytic Fusion Proteins.Biomedicines · 2018Review
- Granzyme B enters the mitochondria in a Sam50-, Tim22- and mtHsp70-dependent manner to induce apoptosis.Cell death and differentiation · 2017Article
- Antimalarial activity of granzyme B and its targeted delivery by a granzyme B-single-chain Fv fusion protein.Antimicrobial agents and chemotherapy · 2015Article
- Whole genome sequencing of SIV-infected macaques identifies candidate loci that may contribute to host control of virus replication.Genome biology · 2014Article
- The perforin pore facilitates the delivery of cationic cargos.The Journal of biological chemistry · 2014Article
- Review
- Conservation of the extended substrate specificity profiles among homologous granzymes across species.Molecular & cellular proteomics : MCP · 2013Article
- Mouse granzyme A induces a novel death with writhing morphology that is mechanistically distinct from granzyme B-induced apoptosis.Cell death and differentiation · 2013Article
- Granzyme B cleaves decorin, biglycan and soluble betaglycan, releasing active transforming growth factor-β1.PloS one · 2012Article
- Granzyme M: characterization with sites of post-translational modification and specific sites of interaction with substrates and inhibitors.Molecular biology reports · 2011Article
- Toxoplasma gondii inhibits granzyme B-mediated apoptosis by the inhibition of granzyme B function in host cells.International journal for parasitology · 2011Article
- Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Granzyme B (GrB) is a key effector of cytotoxic lymphocyte-mediated cell death. It is delivered to target cells bound to the proteoglycan serglycin, but how it crosses the plasma membrane and accesses substrates in the cytoplasm is poorly understood. Here we identify two cationic sequences on GrB that facilitate its binding and uptake. Mutation of cationic sequence 1 (cs1) prevents accumulation of GrB in a distinctive intracellular compartment and reduces cytotoxicity 20-fold. Mutation of cs2 reduces accumulation in this intracellular compartment and cytotoxicity two- to threefold. We also show that GrB-mediated cytotoxicity is abrogated by heparin and that target cells deficient in cell surface sulfate or glycosaminoglycans resist GrB. However, heparin does not completely prevent GrB internalization and chondroitin 4-sulfate does not inhibit cytotoxicity, suggesting that glycosaminoglycans are not essential GrB receptors. We propose that GrB enters cells by nonselective adsorptive pinocytosis, exchanging from chondroitin sulfate on serglycin to anionic components of the cell surface. In this electrostatic "exchange-adsorption" model, cs1 and cs2 participate in binding of GrB to the cell surface, thereby promoting its uptake and eventual release into the cytoplasm.
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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.