ArticleThe Journal of experimental medicine2012
RAG-induced DNA double-strand breaks signal through Pim2 to promote pre-B cell survival and limit proliferation.
Article in The Journal of experimental medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 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.
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Who cites it
33 citing papers in PubMed, 51 citations in OpenAlex.
- RAG suppresses group 2 innate lymphoid cells.eLife · 2025Article
- ATM-dependent Phosphorylation of Nemo SQ Motifs Is Dispensable for Nemo-mediated Gene Expression Changes in Response to DNA Double-Strand Breaks.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- MYSM1 attenuates DNA damage signals triggered by physiologic and genotoxic DNA breaks.The Journal of allergy and clinical immunology · 2024Article
- Article
- PIM Kinase Inhibition Attenuates the Malignant Progression of Metastatic Hepatoblastoma.International journal of molecular sciences · 2023Article
- An overview of pim kinase as a target in multiple myeloma.Cancer medicine · 2023Review
- Nuclease-independent functions of RAG1 direct distinct DNA damage responses in B cells.EMBO reports · 2023Article
- The RAG1 Ubiquitin Ligase Domain Stimulates Recombination of TCRβ and TCRα Genes and Influences Development of αβ T Cell Lineages.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Nemo-Dependent, ATM-Mediated Signals from RAG DNA Breaks atJournal of immunology (Baltimore, Md. : 1950) · 2022Article
- Assessing DNA Damage Responses Using B Lymphocyte Cultures.Methods in molecular biology (Clifton, N.J.) · 2022Article
- The RAG1 N-terminal region regulates the efficiency and pathways of synapsis for V(D)J recombination.The Journal of experimental medicine · 2021Article
- RAG enhances BCR-ABL1-positive leukemic cell growth through its endonuclease activity in vitro and in vivo.Cancer science · 2021Article
- Protein kinase PIM2: A simple PIM family kinase with complex functions in cancer metabolism and therapeutics.Journal of Cancer · 2021Review
- Function and Molecular Mechanism of the DNA Damage Response in Immunity and Cancer Immunotherapy.Frontiers in immunology · 2021Review
- DNA double-strand breaks induce H2Ax phosphorylation domains in a contact-dependent manner.Nature communications · 2020Article
- The role of Pim kinase in immunomodulation.American journal of cancer research · 2020Review
- RAG-Mediated DNA Breaks Attenuate PU.1 Activity in Early B Cells through Activation of a SPIC-BCLAF1 Complex.Cell reports · 2019Article
- At the intersection of DNA damage and immune responses.Nature reviews. Immunology · 2019Review
- The miR-15 family reinforces the transition from proliferation to differentiation in pre-B cells.EMBO reports · 2017Article
- V(D)J Recombination Exploits DNA Damage Responses to Promote Immunity.Trends in genetics : TIG · 2017Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Interleukin 7 (IL-7) promotes pre-B cell survival and proliferation by activating the Pim1 and Akt kinases. These signals must be attenuated to induce G1 cell cycle arrest and expression of the RAG endonuclease, which are both required for IgL chain gene rearrangement. As lost IL-7 signals would limit pre-B cell survival, how cells survive during IgL chain gene rearrangement remains unclear. We show that RAG-induced DNA double-strand breaks (DSBs) generated during IgL chain gene assembly paradoxically promote pre-B cell survival. This occurs through the ATM-dependent induction of Pim2 kinase expression. Similar to Pim1, Pim2 phosphorylates BAD, which antagonizes the pro-apoptotic function of BAX. However, unlike IL-7 induction of Pim1, RAG DSB-mediated induction of Pim2 does not drive proliferation. Rather, Pim2 has antiproliferative functions that prevent the transit of pre-B cells harboring RAG DSBs from G1 into S phase, where these DNA breaks could be aberrantly repaired. Thus, signals from IL-7 and RAG DSBs activate distinct Pim kinase family members that have context-dependent activities in regulating pre-B cell proliferation and survival.
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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.