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dc.contributor.authorMajdalawieh, Amin
dc.contributor.authorZhang, Lei
dc.contributor.authorRo, Hyo-Sung
dc.date.accessioned2022-11-28T09:52:06Z
dc.date.available2022-11-28T09:52:06Z
dc.date.issued2007
dc.identifier.citationMajdalawieh A, Zhang L, Ro HS. (2007) Adipocyte enhancer-binding protein-1 promotes macrophage inflammatory responsiveness by up-regulating NF-κB via IκBα negative regulation. Molecular Biology of the Cell 18(3):930-942. https://doi.org/10.1091/mbc.e06-03-0217.en_US
dc.identifier.issn1939-4586
dc.identifier.urihttp://hdl.handle.net/11073/25064
dc.description.abstractNuclear factor κB (NF-κB) subunits comprise a family of eukaryotic transcription factors that are critically involved in cell proliferation, inflammation, and apoptosis. Under basal conditions, NF-κB subunits are kept under inhibitory regulation by physical interaction with NF-κB inhibitors (IκB subunits) in the cytosol. Upon stimulation, IκB subunits become phosphorylated, ubiquitinated, and subsequently degraded, allowing NF-κB subunits to translocate to the nucleus and bind as dimers to κB responsive elements of target genes. Previously, we have shown that AEBP1 enhances macrophage inflammatory responsiveness by inducing the expression of various proinflammatory mediators. Herein, we provide evidence suggesting that AEBP1 manifests its proinflammatory function by up-regulating NF-κB activity via hampering IκBα, but not IκBβ, inhibitory function through protein–protein interaction mediated by the discoidin-like domain (DLD) of AEBP1. Such interaction renders IκBα susceptible to enhanced phosphorylation and degradation, subsequently leading to augmented NF-κB activity. Collectively, we propose a novel molecular mechanism whereby NF-κB activity is modulated by means of protein–protein interaction involving AEBP1 and IκBα. Moreover, our study provides a plausible mechanism explaining the differential regulatory functions exhibited by IκBα and IκBβ in various cell types. We speculate that AEBP1 may serve as a potential therapeutic target for the treatment of various chronic inflammatory diseases and cancer.en_US
dc.description.sponsorshipCanadian Institute of Health Research (CIHR)en_US
dc.description.sponsorshipNatural Science and Engineering Research Council (NSERC)en_US
dc.language.isoen_USen_US
dc.publisherThe American Society for Cell Biologyen_US
dc.relation.urihttps://doi.org/10.1091/mbc.e06-03-0217en_US
dc.titleAdipocyte Enhancer-binding Protein-1 Promotes Macrophage Inflammatory Responsiveness by Up-Regulating NF-κB via IκBα Negative Regulationen_US
dc.typeArticleen_US
dc.typePeer-Revieweden_US
dc.typePublished versionen_US
dc.identifier.doi10.1091/mbc.e06-03-0217


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