ArticleThe Journal of experimental medicine2012
FoxO1 induces Ikaros splicing to promote immunoglobulin gene recombination.
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 36 papers.
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Who cites it
36 citing papers in PubMed, 62 citations in OpenAlex.
- Multifaceted roles ofFrontiers in oncology · 2024Review
- IKAROS Family Transcription Factors in Lymphocyte Differentiation and Function.Advances in experimental medicine and biology · 2024Review
- IKAROS in Acute Leukemia: A Positive Influencer or a Mean Hater?International journal of molecular sciences · 2023Review
- B-cell antigen receptor expression and phosphatidylinositol 3-kinase signaling regulate genesis and maintenance of mouse chronic lymphocytic leukemia.Haematologica · 2022Article
- The miR-26 family regulates early B cell development and transformation.Life science alliance · 2022Article
- The Small GTPase RHOA Links SLP65 Activation to PTEN Function in Pre B Cells and Is Essential for the Generation and Survival of Normal and Malignant B Cells.Frontiers in immunology · 2022Article
- Ikaros Proteins in Tumor: Current Perspectives and New Developments.Frontiers in molecular biosciences · 2021Review
- It Takes Three Receptors to Raise a B Cell.Trends in immunology · 2020Review
- Article
- Pten controls B-cell responsiveness and germinal center reaction by regulating the expression of IgD BCR.The EMBO journal · 2019Article
- Exploring the RNA Gap for Improving Diagnostic Yield in Primary Immunodeficiencies.Frontiers in genetics · 2019Review
- PI3K-Mediated Blimp-1 Activation Controls B Cell Selection and Homeostasis.Cell reports · 2018Article
- Potent antitumor effect of combination therapy with sub-optimal doses of Akt inhibitors and pomalidomide plus dexamethasone in multiple myeloma.Oncology letters · 2018Article
- PI3K induces B-cell development and regulates B cell identity.Scientific reports · 2018Article
- Discrete roles and bifurcation of PTEN signaling and mTORC1-mediated anabolic metabolism underlie IL-7-driven B lymphopoiesis.Science advances · 2018Article
- PTEN-Regulated AID Transcription in Germinal Center B Cells Is Essential for the Class-Switch Recombination and IgG Antibody Responses.Frontiers in immunology · 2018Article
- Uncovering the Role of RNA-Binding Proteins in Gene Expression in the Immune System.Frontiers in immunology · 2018Review
- The c-Myc/miR17-92/PTEN Axis Tunes PI3K Activity to Control Expression of Recombination Activating Genes in Early B Cell Development.Frontiers in immunology · 2018Article
- Article
- Splicing in immune cells-mechanistic insights and emerging topics.International immunology · 2017Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Somatic rearrangement of immunoglobulin (Ig) genes is a key step during B cell development. Using pro-B cells lacking the phosphatase Pten (phosphatase and tensin homolog), which negatively regulates phosphoinositide-3-kinase (PI3K) signaling, we show that PI3K signaling inhibits Ig gene rearrangement by suppressing the expression of the transcription factor Ikaros. Further analysis revealed that the transcription factor FoxO1 is crucial for Ikaros expression and that PI3K-mediated down-regulation of FoxO1 suppresses Ikaros expression. Interestingly, FoxO1 did not influence Ikaros transcription; instead, FoxO1 is essential for proper Ikaros mRNA splicing, as FoxO1-deficient cells contain aberrantly processed Ikaros transcripts. Moreover, FoxO1-induced Ikaros expression was sufficient only for proximal V(H) to DJ(H) gene rearrangement. Simultaneous expression of the transcription factor Pax5 was needed for the activation of distal V(H) genes; however, Pax5 did not induce any Ig gene rearrangement in the absence of Ikaros. Together, our results suggest that ordered Ig gene rearrangement is regulated by distinct activities of Ikaros, which mediates proximal V(H) to DJ(H) gene rearrangement downstream of FoxO1 and cooperates with Pax5 to activate the rearrangement of distal V(H) genes.
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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.