title: MafK positively regulates NF-κB activity by enhancing CBP-mediated p65 acetylation.
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.
authors.affiliation: 1] Department of Agrofood Resources, National Academy of Agricultural Science, RDA, Suwon, Gyeonggi-do 441-853, Republic of Korea [2] Department of Biotechnology & Bioengineering, Sungkyunkwan University, Suwon, Gyeonggi-do 440-746, Republic of Korea.
authors.forename: Yu-Jin
authors.initials: YJ
authors.lastname: Hwang
authors.forename: Eun-Woo
authors.initials: EW
authors.lastname: Lee
authors.forename: Jaewhan
authors.initials: J
authors.lastname: Song
authors.forename: Haeng-Ran
authors.initials: HR
authors.lastname: Kim
authors.forename: Young-Chun
authors.initials: YC
authors.lastname: Jun
authors.forename: Kyung-A
authors.initials: KA
authors.lastname: Hwang
mesh_terms: D000107:Acetylation; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D005688:Galactosamine / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000378:metabolism; D050985:MafK Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects; D050880:p300-CBP Transcription Factors / Q000378:metabolism*
chemical_list: D016209:Interleukin-8; D008070:Lipopolysaccharides; C494695:MAFK protein, human; D050985:MafK Transcription Factor; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495635:NFE2L2 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D005688:Galactosamine; D050880:p300-CBP Transcription Factors