ArticleThe American journal of pathology2016
SAG/Rbx2-Dependent Neddylation Regulates T-Cell Responses.
Article in The American journal of pathology, 2016. 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, 34 citations in OpenAlex.
- Protein neddylation as a therapeutic target: challenges and opportunities.The Journal of clinical investigation · 2026Review
- Low-Dose MLN4924 Enhances SH-SY5Y Cell Viability and Migration by Targeting SOCS3 Signaling.Doklady. Biochemistry and biophysics · 2025Article
- Protein neddylation in lung tumorigenesis: Target validation and targeted therapy.Fundamental research · 2025Review
- The NAE1-mediated neddylation operates as an essential post-translational modification checkpoint for effector CD8Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- E3 Ligase Rbx1 Orchestrates Thymus Development and Fate Determination of αβ-γδ T Cells.Research (Washington, D.C.) · 2025Article
- Targeting neddylation and sumoylation in chemoresistant triple negative breast cancer.NPJ breast cancer · 2024Article
- Protein neddylation and its role in health and diseases.Signal transduction and targeted therapy · 2024Review
- Neddylation is a novel therapeutic target for lupus by regulating double negative T cell homeostasis.Signal transduction and targeted therapy · 2024Article
- The Cullin-RING Ligase Family in Immune Regulation.Advances in experimental medicine and biology · 2024Review
- Pharmacologic targeting of Nedd8-activating enzyme reinvigorates T-cell responses in lymphoid neoplasia.Leukemia · 2023Article
- Neddylation Regulation of Immune Responses.Research (Washington, D.C.) · 2023Review
- The Ube2m-Rbx1 neddylation-Cullin-RING-Ligase proteins are essential for the maintenance of Regulatory T cell fitness.Nature communications · 2022Article
- An integrative pan-cancer analysis revealing the difference in small ring finger family of SCF E3 ubiquitin ligases.Frontiers in immunology · 2022Article
- Association Between Neddylation and Immune Response.Frontiers in cell and developmental biology · 2022Review
- Neddylation and anti-tumor immunity.Oncotarget · 2021Article
- Targeting neddylation E2s: a novel therapeutic strategy in cancer.Journal of hematology & oncology · 2021Review
- Cell type-specific transcriptomics identifies neddylation as a novel therapeutic target in multiple sclerosis.Brain : a journal of neurology · 2021Article
- The pivotal roles of neddylation pathway in immunoregulation.Immunity, inflammation and disease · 2020Review
- Neddylation: A Versatile Pathway Takes on Chronic Liver Diseases.Frontiers in medicine · 2020Review
- Neddylation: a novel modulator of the tumor microenvironment.Molecular cancer · 2019Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 2 countries.
Funding
Abstract
Neddylation is a crucial post-translational modification that depends on the E3 cullin ring ligase (CRL). The E2-adapter component of the CRL, sensitive to apoptosis gene (SAG), is critical for the function of CRL-mediated ubiquitination; thus, the deletion of SAG regulates neddylation. We examined the role of SAG-dependent neddylation in T-cell-mediated immunity using multiple approaches: a novel T-cell-specific, SAG genetic knockout (KO) and chemical inhibition with small-molecule MLN4924. The KO animals were viable and showed phenotypically normal mature T-cell development. However, in vitro stimulation of KO T cells revealed significantly decreased activation, proliferation, and T-effector cytokine release, compared with WT. Using in vivo clinically relevant models of allogeneic bone marrow transplantation also demonstrated reduced proliferation and effector cytokine secretion associated with markedly reduced graft-versus-host disease. Similar in vitro and in vivo results were observed with the small-molecule inhibitor of neddylation, MLN4924. Mechanistic studies demonstrated that SAG-mediated effects in T cells were concomitant with an increase in suppressor of cytokine signaling, but not NF-κB translocation. Our studies suggest that SAG is a novel molecular target that regulates T-cell responses and that inhibiting neddylation with the clinically available small-molecule MLN4924 may represent a novel strategy to mitigate T-cell-mediated immunopathologies, such as graft-versus-host disease.
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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.