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J Biol Chem. 2008 Feb 1;283(5):2654-62. Epub 2007 Nov 28.

B-cell receptor activation induces BIC/miR-155 expression through a conserved AP-1 element.

Author information

1
Department of Pathology, Tulane Health Sciences Center and Tulane Cancer Center, New Orleans, LA 70112, USA.

Abstract

microRNA-155 is an oncogenic microRNA that has been shown to be critical for B-cell maturation and immunoglobulin production in response to antigen. In line with its function in B-cell activation, miR-155, and its primary transcript, B-cell integration cluster (BIC), is induced by B-cell receptor (BCR) cross-linking. Using pharmacological inhibitors in the human B-cell line, Ramos, we show that activation of BIC and miR-155 expression by BCR signaling occurs through the extracellular signaling-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) pathways but not the p38 pathway. BCR activation results in the induction of c-Fos, FosB, and JunB, and expression of these are suppressed by ERK and JNK inhibitors. Reporter analysis established a key role for a conserved AP-1 site approximately 40 bp upstream from the site of initiation but not an upstream NF-kappaB site or a putative c-Ets located at the site of initiation. Lastly, chromatin immunoprecipitation analysis demonstrated the recruitment of FosB and JunB to the miR-155 promoter following BCR activation. These results identify key determinants of BCR-mediated signaling that lead to the induction of BIC/miR-155.

PMID:
18048365
PMCID:
PMC2810639
DOI:
10.1074/jbc.M708218200
[Indexed for MEDLINE]
Free PMC Article

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