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Publication : miR-29 Sustains B Cell Survival and Controls Terminal Differentiation via Regulation of PI3K Signaling.

First Author  Hines MJ Year  2020
Journal  Cell Rep Volume  33
Issue  9 Pages  108436
PubMed ID  33264610 Mgi Jnum  J:304317
Mgi Id  MGI:6694826 Doi  10.1016/j.celrep.2020.108436
Citation  Hines MJ, et al. (2020) miR-29 Sustains B Cell Survival and Controls Terminal Differentiation via Regulation of PI3K Signaling. Cell Rep 33(9):108436
abstractText  The phosphatidylinositol 3-kinase (PI3K) signaling cascade downstream of the B cell receptor (BCR) signalosome is essential for B cell maturation. Proper signaling strength is maintained through the PI3K negative regulator phosphatase and tensin homolog (PTEN). Although a role for microRNA (miRNA)-dependent control of the PTEN-PI3K axis has been described, the contribution of individual miRNAs to the regulation of this crucial signaling modality in mature B lymphocytes remains to be elucidated. Our analyses reveal that ablation of miR-29 specifically in B lymphocytes results in an increase in PTEN expression and dampening of the PI3K pathway in mature B cells. This dysregulation has a profound impact on the survival of B lymphocytes and results in increased class switch recombination and decreased plasma cell differentiation. Furthermore, we demonstrate that ablation of one copy of Pten is sufficient to ameliorate the phenotypes associated with miR-29 loss. Our data suggest a critical role for the miR-29-PTEN-PI3K regulatory axis in mature B lymphocytes.
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