ArticleThe EMBO journal1997
Perforin is activated by a proteolytic cleavage during biosynthesis which reveals a phospholipid-binding C2 domain.
Article in The EMBO journal, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
57 citing papers in PubMed, 197 citations in OpenAlex.
- Anchoring of perforin-2 via the transmembrane domain is required for antigen escape into the cytosol.The EMBO journal · 2026Article
- Expression and localization of lysosomal-associated membrane protein 1- and perforin-based hybrid molecules in the murine cytotoxic T cell line CTLL-2.Cytotechnology · 2025Article
- Ammonia Suppresses the Antitumor Activity of Natural Killer Cells and T Cells by Decreasing Mature Perforin.Cancer research · 2025Article
- Structural basis for the pore-forming activity of a complement-like toxin.Science advances · 2025Article
- Cytotoxic T lymphocytes require transcription for infiltration but not target cell lysis.EMBO reports · 2023Article
- Natural killer cell immunotherapy in glioblastoma.Discover oncology · 2022Review
- Perforin: An intriguing protein in allograft rejection immunology (Review).Experimental and therapeutic medicine · 2022Review
- The pore conformation of lymphocyte perforin.Science advances · 2022Article
- ALFA-PRF: a novel approach to detect murine perforin release from CTLs into the immune synapse.Frontiers in immunology · 2022Article
- Locked and Loaded: Mechanisms Regulating Natural Killer Cell Lytic Granule Biogenesis and Release.Frontiers in immunology · 2022Review
- Human CD4+ T-Cell Clone Expansion Leads to the Expression of the Cysteine Peptidase Inhibitor Cystatin F.International journal of molecular sciences · 2021Article
- Extracellular Cystatin F Is Internalised by Cytotoxic T Lymphocytes and Decreases Their Cytotoxicity.Cancers · 2020Article
- Review
- Knocking 'em Dead: Pore-Forming Proteins in Immune Defense.Annual review of immunology · 2020Review
- To Kill But Not Be Killed: Controlling the Activity of Mammalian Pore-Forming Proteins.Frontiers in immunology · 2020Review
- Cystatin F as a regulator of immune cell cytotoxicity.Cancer immunology, immunotherapy : CII · 2018Review
- Article
- Regulation of perforin activation and pre-synaptic toxicity through C-terminal glycosylation.EMBO reports · 2017Article
- Antigen-specific CD8Nature communications · 2017Article
- [Expression of porforin and granzyme B in familial hemophagocytic lymphohistiocytosis].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Perforin is a secreted protein synthesized by activated cytotoxic T lymphocytes (CTL) and natural killer (NK) cells. It is a key component of the lytic machinery of these cells, being able to insert into the plasma membrane of targeted cells, forming a pore which leads to their destruction. Here we analyse the synthesis, processing and intracellular transport of perforin in the NK cell line YT. Perforin is synthesized as a 70 kDa inactive precursor which is cleaved at the C-terminus to yield a 60 kDa active form. This proteolytic cleavage occurs in an acidic compartment and can be inhibited by incubation of the cells in ammonium chloride, concanamycin A, leupeptin and E-64. The increased lytic activity of the cleaved form can be demonstrated by killing assays in which cleavage of the pro-piece is inhibited. Epitope mapping reveals that cleavage of the pro-piece occurs at the boundary of a C2 domain, which we show is able to bind phospholipid membranes in a calcium-dependent manner. We propose that removal of the pro-piece, which contains a bulky glycan, allows the C2 domain to interact with phospholipid membranes and initiate perforin pore formation.
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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.