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J Immunol. 2012 Jun 1;188(11):5521-7. doi: 10.4049/jimmunol.1200133. Epub 2012 Apr 30.

CD40 stimulates a "feed-forward" NF-κB-driven molecular pathway that regulates IFN-β expression in carcinoma cells.

Author information

1
Molecular and Cellular Biology Laboratory, Division of Basic Sciences, University of Crete Medical School, 71003 Heraklion, Crete, Greece.

Abstract

IFN-β and the CD40L (CD154) share important roles in the antiviral and antitumor immune responses. In this study, we show that CD40 receptor occupancy results in IFN-β upregulation through an unconventional "feed-forward" mechanism, which is orchestrated by canonical NF-κB and involves the sequential de novo synthesis of IFN regulatory factor (IRF)1 and Viperin (RSAD2), an IRF1 target. RelA (p65) NF-κB, IRF1, and Viperin-dependent IRF7 binding to the IFN-β promoter largely controls its activity. However, full activation of IFN-β also requires the parallel engagement of noncanonical NF-κB2 signaling leading to p52 recruitment to the IFN-β promoter. These data define a novel link between CD40 signaling and IFN-β expression and provide a telling example of how signal propagation can be exploited to ensure efficient regulation of gene expression.

PMID:
22547704
DOI:
10.4049/jimmunol.1200133
[Indexed for MEDLINE]
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