title: CD40 stimulates a "feed-forward" NF-κB-driven molecular pathway that regulates IFN-β expression in carcinoma cells.
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.
authors.affiliation: Molecular and Cellular Biology Laboratory, Division of Basic Sciences, University of Crete Medical School, 71003 Heraklion, Crete, Greece.
authors.forename: Aristides
authors.initials: A
authors.lastname: Moschonas
authors.forename: Marina
authors.initials: M
authors.lastname: Ioannou
authors.forename: Aristides G
authors.initials: AG
authors.lastname: Eliopoulos
mesh_terms: D019013:CD40 Antigens / Q000235:genetics / Q000502:physiology*; D002277:Carcinoma / Q000235:genetics / Q000276:immunology / Q000473:pathology; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D025461:Feedback, Physiological; D005786:Gene Expression Regulation / Q000276:immunology; D057809:HEK293 Cells; D006801:Humans; D016899:Interferon-beta / Q000096:biosynthesis* / Q000235:genetics; D016328:NF-kappa B / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology
chemical_list: D019013:CD40 Antigens; D016328:NF-kappa B; D016899:Interferon-beta