ArticleThe Journal of biological chemistry2014
c-Rel regulates Ezh2 expression in activated lymphocytes and malignant lymphoid cells.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 35 citations in OpenAlex.
- Article
- Chemotherapy with a molecular rational basis, pentoxifylline as a promising antitumor drug.Annals of medicine and surgery (2012) · 2025Review
- Epigenetic reprogramming of T cells: unlocking new avenues for cancer immunotherapy.Cancer metastasis reviews · 2024Review
- EZH2: Its regulation and roles in immune disturbance of SLE.Frontiers in pharmacology · 2022Review
- Insights into high-risk multiple myeloma from an analysis of the role of PHF19 in cancer.Journal of experimental & clinical cancer research : CR · 2021Review
- Migration and Adhesion of B-Lymphocytes to Specific Microenvironments in Mantle Cell Lymphoma: Interplay between Signaling Pathways and the Epigenetic Landscape.International journal of molecular sciences · 2021Review
- Full spectrum of clonal haematopoiesis-driver mutations in chronic heart failure and their associations with mortality.ESC heart failure · 2021Article
- c-Rel Is the Pivotal NF-κB Subunit in Germinal Center Diffuse Large B-Cell Lymphoma: A LYSA Study.Frontiers in oncology · 2021Article
- Genetic Predictors of Mortality in Patients with Multiple Myeloma.The application of clinical genetics · 2021Review
- c-Rel orchestrates energy-dependent epithelial and macrophage reprogramming in fibrosis.Nature metabolism · 2020Article
- Transcriptional Control of Regulatory T Cells in Cancer: Toward Therapeutic Targeting?Cancers · 2020Review
- Role of Polycomb Complexes in Normal and Malignant Plasma Cells.International journal of molecular sciences · 2020Review
- Regulation of B-cell function by NF-kappaB c-Rel in health and disease.Cellular and molecular life sciences : CMLS · 2020Review
- EZH2 as a Regulator of CD8+ T Cell Fate and Function.Frontiers in immunology · 2020Review
- EZH2 abnormalities in lymphoid malignancies: underlying mechanisms and therapeutic implications.Journal of hematology & oncology · 2019Review
- Treg programming and therapeutic reprogramming in cancer.Immunology · 2019Review
- Targeting EZH2 in Multiple Myeloma-Multifaceted Anti-Tumor Activity.Epigenomes · 2018Article
- The biological significance of histone modifiers in multiple myeloma: clinical applications.Blood cancer journal · 2018Review
- Targeting EZH2 Reprograms Intratumoral Regulatory T Cells to Enhance Cancer Immunity.Cell reports · 2018Article
- An Autocrine TNFα-Tumor Necrosis Factor Receptor 2 Loop Promotes Epigenetic Effects Inducing Human Treg StabilityFrontiers in immunology · 2018Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The polycomb group protein Ezh2 is a histone methyltransferase that modifies chromatin structure to alter gene expression during embryonic development, lymphocyte activation, and tumorigenesis. The mechanism by which Ezh2 expression is regulated is not well defined. In the current study, we report that c-Rel is a critical activator of Ezh2 transcription in lymphoid cells. In activated primary murine B and T cells, plus human leukemia and multiple myeloma cell lines, recruitment of c-Rel to the first intron of the Ezh2 locus promoted Ezh2 mRNA expression. This up-regulation was abolished in activated c-Rel-deficient lymphocytes and by c-Rel knockdown in Jurkat T cells. Treatment of malignant cells with the c-Rel inhibitor pentoxifylline not only reduced c-Rel nuclear translocation and Ezh2 expression, but also enhanced their sensitivity to the Ezh2-specific drug, GSK126 through increased growth inhibition and cell death. In summary, our demonstration that c-Rel regulates Ezh2 expression in lymphocytes and malignant lymphoid cells reveals a novel transcriptional network in transformed lymphoid cells expressing high levels of Ezh2 that provides a molecular justification for combinatorial drug therapy.
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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.