ArticleBlood2015
NF-κB and AKT signaling prevent DNA damage in transformed pre-B cells by suppressing RAG1/2 expression and activity.
Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- From PGT-M discovery to mechanism: functional validation of novel compound heterozygous RAG1 mutations in severe combined immunodeficiency.Journal of assisted reproduction and genetics · 2026Article
- FOXO1 phosphorylation as a context-dependent molecular switch in cancer: from mechanisms to precision therapy.World journal of surgical oncology · 2025Review
- FoxO1 signaling in B cell malignancies and its therapeutic targeting.FEBS letters · 2025Review
- O-GlcNAcylation mediates HActa pharmacologica Sinica · 2024Article
- First Report of FARSA in the Regulation of Cell Cycle and Survival in Mantle Cell Lymphoma Cells via PI3K-AKT and FOXO1-RAG1 Axes.International journal of molecular sciences · 2023Article
- Radiofrequency EMF irradiation effects on pre-B lymphocytes undergoing somatic recombination.Scientific reports · 2021Article
- Forkhead Box Protein O1: Functional Diversity and Post-Translational Modification, a New Therapeutic Target?Drug design, development and therapy · 2021Review
- AKT signaling restrains tumor suppressive functions of FOXO transcription factors and GSK3 kinase in multiple myeloma.Blood advances · 2020Article
- Article
- The NEDD8-activating enzyme inhibitor MLN4924 induces DNA damage in Ph+ leukemia and sensitizes for ABL kinase inhibitors.Cell cycle (Georgetown, Tex.) · 2019Article
- Fine-tuning of FOXO3A in cHL as a survival mechanism and a hallmark of abortive plasma cell differentiation.Blood · 2018Article
- Molecular processes involved in B cell acute lymphoblastic leukaemia.Cellular and molecular life sciences : CMLS · 2018Review
- The Complex Interplay between DNA Injury and Repair in Enzymatically Induced Mutagenesis and DNA Damage in B Lymphocytes.International journal of molecular sciences · 2017Review
- Immature Lymphocytes InhibitJournal of immunology (Baltimore, Md. : 1950) · 2017Article
- Radiosensitizing effect of diosmetin on radioresistant lung cancer cells via Akt signaling pathway.PloS one · 2017Article
- Kinesin Family Member C1 Increases Temozolomide Resistance of Glioblastoma Through Promoting DNA Damage Repair.Cell transplantationArticle
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In developing lymphocytes, expression and activity of the recombination activation gene protein 1 (RAG1) and RAG2 endonuclease complex is tightly regulated to ensure ordered recombination of the immunoglobulin genes and to avoid genomic instability. Aberrant RAG activity has been implicated in the generation of secondary genetic events in human B-cell acute lymphoblastic leukemias (B-ALLs), illustrating the oncogenic potential of the RAG complex. Several layers of regulation prevent collateral genomic DNA damage by restricting RAG activity to the G1 phase of the cell cycle. In this study, we show a novel pathway that suppresses RAG expression in cycling-transformed mouse pre-B cells and human pre-B B-ALL cells that involves the negative regulation of FOXO1 by nuclear factor κB (NF-κB). Inhibition of NF-κB in cycling pre-B cells resulted in upregulation of RAG expression and recombination activity, which provoked RAG-dependent DNA damage. In agreement, we observe a negative correlation between NF-κB activity and the expression of RAG1, RAG2, and TdT in B-ALL patients. Our data suggest that targeting NF-κB in B-ALL increases the risk of RAG-dependent genomic instability.
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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.