ArticleInternational journal of molecular sciences2021
Role of ADAM10 and ADAM17 in Regulating CD137 Function.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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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.
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Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
- Cell surface remodeling caused by the loss of the flippase subunit TMEM30A in immune cells.Journal of cell science · 2026Article
- Development of Diagnostic Models and Biomarker Identification for Type 1 Leptomeningeal Metastasis in Lung Adenocarcinoma Using Olink: Exploratory Cohort Study with Internal Temporal Validation.Molecular diagnosis & therapy · 2026Article
- Lipid-Facilitated Opening of the ADAM10 Sheddase Revealed by Enhanced Sampling Simulations.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Multiple roles of ANO6 in tumors, molecular mechanism and its potential therapeutic value.Biochemistry and biophysics reports · 2025Review
- Development and validation of highly sensitive ligand binding assay to measure soluble DLL3 concentration in human serum.Bioanalysis · 2025Article
- A First-in-Human Study of Cinrebafusp Alfa, a HER2/4-1BB Bispecific Molecule, in Patients with HER2-Positive Advanced Solid Malignancies.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Targeting a disintegrin and metalloprotease (ADAM) 17-CD122 axis enhances CD8Signal transduction and targeted therapy · 2024Article
- Metabolic Rewiring in Cancer: Small Molecule Inhibitors in Colorectal Cancer Therapy.Molecules (Basel, Switzerland) · 2024Review
- Soluble CD137: A Potential Prognostic Biomarker in Critically Ill Patients.International journal of molecular sciences · 2023Article
- Soluble CD137 as a dynamic biomarker to monitor agonist CD137 immunotherapies.Journal for immunotherapy of cancer · 2022Article
- Scramblases as Regulators of ProteolyticMembranes · 2022Review
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- Proteolysis dysfunction in the process of aging and age-related diseases.Frontiers in aging · 2022Review
- Phospholipid Scramblases: Role in Cancer Progression and Anticancer Therapeutics.Frontiers in genetics · 2022Review
- Immunomodulatory role of metalloproteinase ADAM17 in tumor development.Frontiers in immunology · 2022Review
- Immunomodulatory role of metalloproteases in cancers: Current progress and future trends.Frontiers in immunology · 2022Review
- A Disintegrin and Metalloproteases (ADAMs): Activation, Regulation and Mechanisms of Catalysis.International journal of molecular sciences · 2021Article
- Construction and Validation of a Novel Pyroptosis-Related Gene Signature to Predict the Prognosis of Uveal Melanoma.Frontiers in cell and developmental biology · 2021Article
- Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Human CD137 (4-1BB), a member of the TNF receptor family, and its ligand CD137L (4-1BBL), are expressed on immune cells and tumor cells. CD137/CD137L interaction mediates bidirectional cellular responses of potential relevance in inflammatory diseases, autoimmunity and oncology. A soluble form of CD137 exists, elevated levels of which have been reported in patients with rheumatoid arthritis and various malignancies. Soluble CD137 (sCD137) is considered to represent a splice variant of CD137. In this report, however, evidence is presented that A Disintegrin and Metalloproteinase (ADAM)10 and potentially also ADAM17 are centrally involved in its generation. Release of sCD137 by transfected cell lines and primary T cells was uniformly inhibitable by ADAM10 inhibition. The shedding function of ADAM10 can be blocked through inhibition of its interaction with surface exposed phosphatidylserine (PS), and this effectively inhibited sCD137 generation. The phospholipid scramblase Anoctamin-6 (ANO6) traffics PS to the outer membrane and thus modifies ADAM10 function. Overexpression of ANO6 increased stimulated shedding, and hyperactive ANO6 led to maximal constitutive shedding of CD137. sCD137 was functionally active and augmented T cell proliferation. Our findings shed new light on the regulation of CD137/CD137L immune responses with potential impact on immunotherapeutic approaches targeting CD137.
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What OpenQuestion holds
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.