ArticleProceedings of the National Academy of Sciences of the United States of America2008
Structural basis for ligand-mediated mouse GITR activation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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
24 citing papers in PubMed, 53 citations in OpenAlex.
- A bioactive soluble recombinant mouse LIGHT promotes effective tumor immune cell infiltration delaying tumor growth.Journal of molecular medicine (Berlin, Germany) · 2025Article
- Exploring the Role of GITR/GITRL Signaling: From Liver Disease to Hepatocellular Carcinoma.Cancers · 2024Review
- Phase IB Study of GITR Agonist Antibody TRX518 Singly and in Combination with Gemcitabine, Pembrolizumab, or Nivolumab in Patients with Advanced Solid Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Optimal target saturation of ligand-blocking anti-GITR antibody IBI37G5 dictates FcγR-independent GITR agonism and antitumor activity.Cell reports. Medicine · 2022Article
- An anti-PD-1-GITR-L bispecific agonist induces GITR clustering-mediated T cell activation for cancer immunotherapy.Nature cancer · 2022Article
- Therapeutic antibody activation of the glucocorticoid-induced TNF receptor by a clustering mechanism.Science advances · 2022Article
- Structures of mouse and human GITR-GITRL complexes reveal unique TNF superfamily interactions.Nature communications · 2021Article
- New emerging targets in cancer immunotherapy: the role of GITR.ESMO open · 2020Review
- A universal reporter cell line for bioactivity evaluation of engineered cytokine products.Scientific reports · 2020Article
- HERA-GITRL activates T cells and promotes anti-tumor efficacy independent of FcγR-binding functionality.Journal for immunotherapy of cancer · 2019Article
- Crystal structure of the m4-1BB/4-1BBL complex reveals an unusual dimeric ligand that undergoes structural changes upon 4-1BB receptor binding.The Journal of biological chemistry · 2019Article
- The promise and challenges of immune agonist antibody development in cancer.Nature reviews. Drug discovery · 2018Review
- Crystal structure of murine 4-1BB and its interaction with 4-1BBL support a role for galectin-9 in 4-1BB signaling.The Journal of biological chemistry · 2018Article
- Principles of antibody-mediated TNF receptor activation.Cell death and differentiation · 2015Review
- Targeting tumor-necrosis factor receptor pathways for tumor immunotherapy.Journal for immunotherapy of cancer · 2014Review
- Correlation of increased blood levels of GITR and GITRL with disease severity in patients with primary Sjögren's syndrome.Clinical & developmental immunology · 2013Article
- The intracellular portion of GITR enhances NGF-promoted neurite growth through an inverse modulation of Erk and NF-κB signalling.Biology open · 2012Article
- Pharmacological modulation of GITRL/GITR system: therapeutic perspectives.British journal of pharmacology · 2012Review
- Modulation of GITR for cancer immunotherapy.Current opinion in immunology · 2012Review
- An isoleucine-zipper motif enhances costimulation of human soluble trimeric GITR ligand.Cellular & molecular immunology · 2010Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Glucocorticoid-induced TNF receptor ligand (GITRL) is a member of the TNF super family (TNFSF). GITRL plays an important role in controlling regulatory T cells. The crystal structure of the mouse GITRL (mGITRL) was determined to 1.8-A resolution. Contrary to the current paradigm that all ligands in the TNFSF are trimeric, mGITRL associates as dimer through a unique C terminus tethering arm. Analytical ultracentrifuge studies revealed that in solution, the recombinant mGITRL exists as monomers at low concentrations and as dimers at high concentrations. Biochemical studies confirmed that the mGITRL dimer is biologically active. Removal of the three terminal residues in the C terminus resulted in enhanced receptor-mediated NF-kappaB activation than by the wild-type receptor complex. However, deletion of the tethering C-terminus arm led to reduced activity. Our studies suggest that the mGITRL may undergo a dynamic population shift among different oligomeric forms via C terminus-mediated conformational changes. We hypothesize that specific oligomeric forms of GITRL may be used as a means to differentially control GITR receptor signaling in diverse cells.
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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.