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The c-Myc/miR17-92/PTEN axis tunes PI3K activity to control expression of recombination activating genes in early B cell development

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Item Type:Article
Title:The c-Myc/miR17-92/PTEN axis tunes PI3K activity to control expression of recombination activating genes in early B cell development
Creators Name:Benhamou, D. and Labi, V. and Getahun, A. and Benchetrit, E. and Dowery, R. and Rajewsky, K. and Cambier, J.C. and Melamed, D.
Abstract:Appropriate PI3K signals generated by the antigen receptor are essential to promote B cell development. Regulation of recombination activating gene (RAG)-1 and RAG-2 expression is one key process that is mediated by PI3K to ensure developmental progression and selection. When PI3K signals are too high or too low, expression of RAGs does not turn off and B cell development is impaired or blocked. Yet, the mechanism which tunes PI3K activity to control RAG expression during B cell development in the bone marrow is unknown. Recently we showed that a c-Myc/miR17-92/PTEN axis regulates PI3K activity for positive and negative selection of immature B cells. Here, we show that the c-Myc/miR17-92/PTEN axis tunes PI3K activity to control the expression of RAGs in proB cells. Using different genetically engineered mouse models we show that impaired function of the c-Myc/miR17-92/PTEN axis alters the PI3K/Akt/Foxo1 pathway to result in dis-regulated expression of RAG and a block in B cell development. Studies using 38c-13 B lymphoma cells, where RAGs are constitutively expressed, suggest that this regulatory effect is mediated post-translationally through Foxo1.
Keywords:B Cell Development, Recombination Activating Gene (RAG), PI3K-AKT Pathway, microRNA, PTEN (Phosphatase and Tensin Homolog), Animals, Mice
Source:Frontiers in Immunology
ISSN:1664-3224
Publisher:Frontiers Media SA (Switzerland)
Volume:9
Page Range:2715
Date:November 2018
Official Publication:https://doi.org/10.3389/fimmu.2018.02715
PubMed:View item in PubMed

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