MafK positively regulates NF-κB 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-kappa B 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-kappa B activity. MafK knockdown reduced NF-kappa B activation, whereas MafK overexpression enhanced NF-kappa B function. MafK mediated p65 acetylation by CBP upon LPS stimulation, thereby facilitating recruitment of p65 to NF-kappa B promoters such as IL-8 and TNF alpha. 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-kappa B activity via CBP-mediated p65 acetylation.