ArticleThe Journal of biological chemistry2014
Rapid degradation of the complement regulator, CD59, by a novel inhibitor.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- Macrophage EHD1 Promotes Inflammation and Stabilizes Sortilin to Accelerate Atherosclerosis.Circulation research · 2026Article
- Bacterial pore-forming toxins: mechanisms and implications for host immunity.Bioscience reports · 2026Review
- Complement system in cancer: friend or foe of immunotherapy.Journal for immunotherapy of cancer · 2026Review
- CD46 and CD59 inhibitors enhance complement-dependent cytotoxicity of anti-CD38 monoclonal antibodies daratumumab and isatuximab in multiple myeloma and other B-cell malignancy cells.Cancer biology & therapy · 2024Article
- Identification and Analysis of Anticancer Therapeutic Targets from the Polysaccharide Krestin (PSK) and Polysaccharopeptide (PSP) Using Inverse Docking.Molecules (Basel, Switzerland) · 2024Article
- Story of Pore-Forming Proteins from Deadly Disease-Causing Agents to Modern Applications with Evolutionary Significance.Molecular biotechnology · 2024Review
- Advances and challenges in understanding endosomal sorting and fission.The FEBS journal · 2023Article
- Receptor-mediated internalization promotes increased endosome size and number in a RAB4- and RAB5-dependent manner.European journal of cell biology · 2023Article
- Contribution of Extracellular Vesicles and Molecular Chaperones in Age-Related Neurodegenerative Disorders of the CNS.International journal of molecular sciences · 2023Review
- Coronin2A links actin-based endosomal processes to the EHD1 fission machinery.Molecular biology of the cell · 2022Article
- Weak Expression of Terminal Complement in Active Antibody-Mediated Rejection of the Kidney.Frontiers in immunology · 2022Article
- Deciphering the Intricate Roles of Radiation Therapy and Complement Activation in Cancer.International journal of radiation oncology, biology, physics · 2020Review
- Pharmacological Targeting of Pore-Forming Toxins as Adjunctive Therapy for Invasive Bacterial Infection.Toxins · 2018Review
- Emerging roles of extracellular vesicles in neurodegenerative disorders: focus on HIV-associated neurological complications.Cell death & disease · 2016Review
- Interplay of endoplasmic reticulum stress and autophagy in neurodegenerative disorders.Autophagy · 2016Review
- The endocytic recycling compartment maintains cargo segregation acquired upon exit from the sorting endosome.Molecular biology of the cell · 2016Article
- Qualitative and quantitative analysis of endocytic recycling.Methods in cell biology · 2015Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
There is increased interest in immune-based monoclonal antibody therapies for different malignancies because of their potential specificity and limited toxicity. The activity of some therapeutic monoclonal antibodies is partially dependent on complement-dependent cytolysis (CDC), in which the immune system surveys for invading pathogens, infected cells, and malignant cells and facilitates their destruction. CD59 is a ubiquitously expressed cell-surface glycosylphosphatidylinositol-anchored protein that protects cells from CDC. However, in certain tumors, CD59 expression is enhanced, posing a significant obstacle for treatment, by hindering effective monoclonal antibody-induced CDC. In this study, we used non-small lung carcinoma cells to characterize the mechanism of a novel CD59 inhibitor: the 114-amino acid recombinant form of the 4th domain of intermedilysin (rILYd4), a pore forming toxin secreted by Streptococcus intermedius. We compared the rates of internalization of CD59 in the presence of rILYd4 or anti-CD59 antibodies and determined that rILYd4 induces more rapid CD59 uptake at early time points. Most significantly, upon binding to rILYd4, CD59 is internalized and undergoes massive degradation in lysosomes within minutes. The remaining rILYd4·CD59 complexes recycle to the PM and are shed from the cell. In comparison, upon internalization of CD59 via anti-CD59 antibody binding, the antibody·CD59 complex is recycled via early and recycling endosomes, mostly avoiding degradation. Our study supports a novel role for rILYd4 in promoting internalization and rapid degradation of the complement inhibitor CD59, and highlights the potential for improving CDC-based immunotherapy.
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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.