Abstract
Reactive oxygen species, produced by oxidative stress, initiate and promote many metabolic diseases through activation/suppression of redox-sensitive transcription factors. NF-κB and Nrf2 are important regulators of oxidation resistance and contribute to the pathogenesis of many diseases. We identified MafK, a novel transcriptional regulator that modulates NF-κB activity. MafK knockdown reduced NF-κB activation, whereas MafK overexpression enhanced NF-κB function. MafK mediated p65 acetylation by CBP upon LPS stimulation, thereby facilitating recruitment of p65 to NF-κB promoters such as IL-8 and TNFα. Consistent with these results, MafK-depleted mice showed prolonged survival with a reduced hepatic inflammatory response after LPS and D-GalN injection. Thus, our findings reveal a novel mechanism by which MafK controls NF-κB activity via CBP-mediated p65 acetylation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylation
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Animals
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Apoptosis / drug effects
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Galactosamine / pharmacology
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Hep G2 Cells
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Humans
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Interleukin-8 / metabolism
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Lipopolysaccharides / toxicity
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Liver / metabolism
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MafK Transcription Factor / antagonists & inhibitors
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MafK Transcription Factor / genetics
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MafK Transcription Factor / metabolism*
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Mice
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NF-E2-Related Factor 2 / antagonists & inhibitors
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NF-E2-Related Factor 2 / genetics
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NF-E2-Related Factor 2 / metabolism
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NF-kappa B / metabolism*
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RNA Interference
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RNA, Messenger / metabolism
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RNA, Small Interfering / metabolism
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Signal Transduction / drug effects
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Transcription Factor RelA / metabolism
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Tumor Necrosis Factor-alpha / pharmacology
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Up-Regulation / drug effects
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p300-CBP Transcription Factors / metabolism*
Substances
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Interleukin-8
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Lipopolysaccharides
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MAFK protein, human
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MafK Transcription Factor
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NF-E2-Related Factor 2
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NF-kappa B
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NFE2L2 protein, human
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RNA, Messenger
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RNA, Small Interfering
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Transcription Factor RelA
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Tumor Necrosis Factor-alpha
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Galactosamine
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p300-CBP Transcription Factors