MafK positively regulates NF-[kappa]B activity by enhancing CBP-mediated p65 acetylation

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 identif...

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Bibliographic Details
Published in:Scientific reports 2013-11, Vol.3, p.3242
Main Authors: Hwang, Yu-jin, Lee, Eun-woo, Song, Jaewhan, Kim, Haeng-ran, Jun, Young-chun, Hwang, Kyung-a
Format: Article
Language:English
Subjects:
Acetylation
Inflammation
Interleukin 8
Lipopolysaccharides
Metabolic disorders
Metabolic rate
NF-κB protein
Oxidative stress
Promoters
Reactive oxygen species
Rodents
Transcription activation
Transcription factors
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Summary: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.
ISSN:2045-2322
DOI:10.1038/srep03242