ArticleJournal of immunology (Baltimore, Md. : 1950)2009
IFN regulatory factor 8 regulates MDM2 in germinal center B cells.
Article in Journal of immunology (Baltimore, Md. : 1950), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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
28 citing papers in PubMed, 43 citations in OpenAlex.
- Targeting metabolic-epigenetic-immune axis in cancer: molecular mechanisms and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- MDM2 inhibitors in cancer immunotherapy: Current status and perspective.Genes & diseases · 2024Review
- Review
- Review
- Altered pathways and targeted therapy in double hit lymphoma.Journal of hematology & oncology · 2022Review
- The roles and regulation of MDM2 and MDMX: it is not just about p53.Genes & development · 2021Review
- Transcriptional regulation of memory B cell differentiation.Nature reviews. Immunology · 2021Review
- IFN-γ and CD38 in Hyperprogressive Cancer Development.Cancers · 2021Review
- Hyperprogressive Disease in Cancers Treated With Immune Checkpoint Inhibitors.Frontiers in pharmacology · 2021Review
- Hyperprogression: A novel response pattern under immunotherapy.Clinical and translational medicine · 2020Review
- Transfer RNA methyltransferase gene NSUN2 mRNA expression modifies the effect of T cell activation score on patient survival in head and neck squamous carcinoma.Oral oncology · 2020Article
- Hyperprogression After Immune-Checkpoint Inhibitor Treatment: Characteristics and Hypotheses.Frontiers in oncology · 2020Review
- Hyperprogression after immunotherapy in patients with malignant tumors of digestive system.BMC cancer · 2019Article
- Lower Interferon Regulatory Factor-8 Expression in Peripheral Myeloid Cells Tracks With Adverse Central Nervous System Outcomes in Treated HIV Infection.Frontiers in immunology · 2019Article
- The Transcriptional Regulation of Germinal Center Formation.Frontiers in immunology · 2018Review
- Hyperprogressors after Immunotherapy: Analysis of Genomic Alterations Associated with Accelerated Growth Rate.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
- Article
- Loss of IRF8 Inhibits the Growth of Diffuse Large B-cell Lymphoma.Journal of Cancer · 2015Article
- A reporter mouse reveals lineage-specific and heterogeneous expression of IRF8 during lymphoid and myeloid cell differentiation.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- Apurinic/apyrimidinic endonuclease 2 regulates the expansion of germinal centers by protecting against activation-induced cytidine deaminase-independent DNA damage in B cells.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
IFN regulatory factor 8 (IRF8) is a transcription factor that affects the differentiation and function of myeloid, dendritic, and B cells. Herein we report that IRF8 regulates the expression of Mdm2, a suppressor of p53-dependent and -independent apoptosis pathways, in germinal center (GC) B cells. In GC B cells of IRF8-deficient mice, Mdm2 transcripts were greatly down-regulated, and MDM2 protein was poorly expressed in GC of Irf8(-/-) mice. Small interfering RNA-induced repression of IRF8 in a GC-derived B cell line resulted in decreased expression of MDM2 at the protein level but increased expression of p53 and p21. We found that IRF8 binds to the Mdm2 P2 promoter, and that cotransfection of an IRF8 expression vector with an Mdm2 reporter construct stimulated significant increases in reporter activity. Additionally, transcripts of the p53 target Pmaip1 (Noxa) were significantly increased in IRF8-deficient GC B cells as well as in the IRF8 knockdown B cell line. Finally, cells deficient in IRF8 exhibited growth suppression and increased sensitivity to apoptosis induced by etoposide or IL-21. These results suggest that by regulating MDM2, IRF8 might allow GC B cells to tolerate physiological DNA breaks that otherwise would trigger apoptosis.
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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.