ArticleBlood2020
Cereblon harnesses Myc-dependent bioenergetics and activity of CD8+ T lymphocytes.
Article in Blood, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 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
14 citing papers in PubMed, 22 citations in OpenAlex.
- Advances in immune microenvironment profiling during multiple myeloma progression and therapy.International journal of hematology · 2026Review
- Combining lenalidomide with IL-2 family of cytokines enhances activating receptor and perforin/granzyme expression in NK cells.PloS one · 2026Article
- Modulating the polyamine/hypusine axis controls generation of CD8+ tissue-resident memory T cells.JCI insight · 2023Article
- The Ubiquitin-Proteasome System in Tumor Metabolism.Cancers · 2023Review
- DDB1 regulates the activation-induced apoptosis of T cells via downregulating the expression of histone methyltransferase SETD7.Medical oncology (Northwood, London, England) · 2023Article
- The Relationship Between the Expression of CRBN in Peripheral Blood and the Severity and Prognosis of Adult Sepsis.International journal of general medicine · 2023Article
- The transcription factor IRF2 drives interferon-mediated CD8Immunity · 2022Article
- T and B cell abnormalities, pneumocystis pneumonia, and chronic lymphocytic leukemia associated with an AIOLOS defect in patients.The Journal of experimental medicine · 2021Article
- Cereblon regulates NK cell cytotoxicity and migration via Rac1 activation.European journal of immunology · 2021Article
- PI3K/Akt Pathway: The Indestructible Role of a Vintage Target as a Support to the Most Recent Immunotherapeutic Approaches.Cancers · 2021Review
- Circ_0114428 Regulates Sepsis-Induced Kidney Injury by Targeting the miR-495-3p/CRBN Axis.Inflammation · 2021Article
- Small-molecule HDAC and Akt inhibitors suppress tumor growth and enhance immunotherapy in multiple myeloma.Journal of experimental & clinical cancer research : CR · 2021Article
- [Research Progress on the Mechanism and Clinical Data of Cereblon in Reversing the Resistance of Lung Cancer to PD-1 Antibody by T cells].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2021Review
- Neurodevelopmental Disorders (NDD) Caused by Genomic Alterations of the Ubiquitin-Proteasome System (UPS): the Possible Contribution of Immune Dysregulation to Disease Pathogenesis.Frontiers in molecular neuroscience · 2021Review
Corrections and comments
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Authors and funding
31 authors at 9 institutions in 2 countries.
Funding
Abstract
Immunomodulatory drugs, such as thalidomide and related compounds, potentiate T-cell effector functions. Cereblon (CRBN), a substrate receptor of the DDB1-cullin-RING E3 ubiquitin ligase complex, is the only molecular target for this drug class, where drug-induced, ubiquitin-dependent degradation of known "neosubstrates," such as IKAROS, AIOLOS, and CK1α, accounts for their biological activity. Far less clear is whether these CRBN E3 ligase-modulating compounds disrupt the endogenous functions of CRBN. We report that CRBN functions in a feedback loop that harnesses antigen-specific CD8+ T-cell effector responses. Specifically, Crbn deficiency in murine CD8+ T cells augments their central metabolism manifested as elevated bioenergetics, with supraphysiological levels of polyamines, secondary to enhanced glucose and amino acid transport, and with increased expression of metabolic enzymes, including the polyamine biosynthetic enzyme ornithine decarboxylase. Treatment with CRBN-modulating compounds similarly augments central metabolism of human CD8+ T cells. Notably, the metabolic control of CD8+ T cells by modulating compounds or Crbn deficiency is linked to increased and sustained expression of the master metabolic regulator MYC. Finally, Crbn-deficient T cells have augmented antigen-specific cytolytic activity vs melanoma tumor cells, ex vivo and in vivo, and drive accelerated and highly aggressive graft-versus-host disease. Therefore, CRBN functions to harness the activation of CD8+ T cells, and this phenotype can be exploited by treatment with drugs.
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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.