ArticleProceedings of the National Academy of Sciences of the United States of America2016
Epigenetic regulation of Kcna3-encoding Kv1.3 potassium channel by cereblon contributes to regulation of CD4+ T-cell activation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 41 citations in OpenAlex.
- Safety considerations for cereblon-recruiting targeted protein degraders.Nature reviews. Drug discovery · 2026Review
- Potassium suppresses allosteric activation of ZAP-70-dependent T cell receptor signaling.The Journal of biological chemistry · 2026Article
- Single-cell RNA sequencing data analysis reveals differential expressions of ion channels in immunity response to pulmonary COVID-19 infection.Biochemical and biophysical research communications · 2026Article
- Lung-specific CRBN knockout attenuates influenza a virus-induced acute lung injury in mice: a potential therapeutic approach.BMC infectious diseases · 2025Article
- Integrative analysis of ASXL family genes reveals ASXL2 as an immunoregulatory molecule in head and neck squamous cell carcinoma.Scientific reports · 2024Article
- Sodium, Potassium-Adenosine Triphosphatase as a Potential Target of the Anti-Tuberculosis Agents, Clofazimine and Bedaquiline.International journal of molecular sciences · 2024Article
- 3,3',4,4'-tetrachlorobiphenyl (PCB77) enhances human Kv1.3 channel currents and alters cytokine production.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2024Article
- DNA methylome in pancreatic cancer identified novel promoter hyper-methylation in NPY and FAIM2 genes associated with poor prognosis in Indian patient cohort.Cancer cell international · 2022Article
- Predicted Immune-Related Genes and Subtypes in Systemic Lupus Erythematosus Based on Immune Infiltration Analysis.Disease markers · 2022Article
- Molecular Mechanisms of Cereblon-Interacting Small Molecules in Multiple Myeloma Therapy.Journal of personalized medicine · 2021Review
- Cereblon: promise and challenges for combating human diseases.Pflugers Archiv : European journal of physiology · 2021Review
- In-depth single-cell analysis of translation-competent HIV-1 reservoirs identifies cellular sources of plasma viremia.Nature communications · 2021Article
- Cereblon Regulates the Proteotoxicity of Tau by Tuning the Chaperone Activity of DNAJA1.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Single-cell multiomics dissection of basal and antigen-specific activation states of CD19-targeted CAR T cells.Journal for immunotherapy of cancer · 2021Article
- Abundant Monovalent Ions as Environmental Signposts for Pathogens during Host Colonization.Infection and immunity · 2021Review
- Article
- [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
- Identification of Immune-Related Key Genes in Ovarian Cancer Based on WGCNA.Frontiers in genetics · 2021Article
- Crbn modulates calcium influx by regulating Orai1 during efferocytosis.Nature communications · 2020Article
- Article
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The role of cereblon (CRBN) in T cells is not well understood. We generated mice with a deletion in Crbn and found cereblon to be an important antagonist of T-cell activation. In mice lacking CRBN, CD4(+) T cells show increased activation and IL-2 production on T-cell receptor stimulation, ultimately resulting in increased potassium flux and calcium-mediated signaling. CRBN restricts T-cell activation via epigenetic modification of Kcna3, which encodes the Kv1.3 potassium channel required for robust calcium influx in T cells. CRBN binds directly to conserved DNA elements adjacent to Kcna3 via a previously uncharacterized DNA-binding motif. Consequently, in the absence of CRBN, the expression of Kv1.3 is derepressed, resulting in increased Kv1.3 expression, potassium flux, and CD4(+) T-cell hyperactivation. In addition, experimental autoimmune encephalomyelitis in T-cell-specific Crbn-deficient mice was exacerbated by increased T-cell activation via Kv1.3. Thus, CRBN limits CD4(+) T-cell activation via epigenetic regulation of Kv1.3 expression.
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