title: Activating transcription factor 3 represses inflammatory responses by binding to the p65 subunit of NF-κB.
abstract: Activating transcription factor 3 (ATF3) is induced by inflammatory responses, cell death, cytokines, and oxidative stress conditions. ATF3 is a negative regulator in the Toll-like receptor 4 signalling pathway. The principal molecule in this pathway is nuclear factor κB (NF-κB) that translocates into the nucleus to initiate the transcription of inflammatory mediators. However, scarce data are available regarding the interaction of ATF3 and p65, a part of the NF-κB dimer. Therefore, we studied the mechanism of regulation of p65 by ATF3 in RAW 264.7 cells. First, LPS-mediated NF-κB activation was confirmed, and then the direct interaction of ATF3 and p65 was observed through immunoprecipitation (IP). The presence of histone deacetylase 1 (HDAC1) was also detected in the complex. In ATF3 deficient cells, NF-κB activity was up-regulated and HDAC1 was not detected by IP. These observations suggest that p65 is attenuated by ATF3 such that ATF3 recruits HDAC1 to the ATF3/p65 complex and facilitates the deacetylation of p65. Likewise, inflammatory response genes were induced by translocated NF-κB in ATF3-deficient cells. Cumulatively, we uncovered a novel mechanism for the negative regulation of NF-κB by ATF3 via direct interaction with p65.
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon, 443-749, Korea.
authors.forename: Ji-Woong
authors.initials: JW
authors.lastname: Kwon
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon, 443-749, Korea.
authors.forename: Hyuk-Kwon
authors.initials: HK
authors.lastname: Kwon
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon, 443-749, Korea.
authors.forename: Hyeon-Jun
authors.initials: HJ
authors.lastname: Shin
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon, 443-749, Korea.
authors.forename: Yong-Min
authors.initials: YM
authors.lastname: Choi
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon, 443-749, Korea.
authors.forename: Muhammad Ayaz
authors.initials: MA
authors.lastname: Anwar
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon, 443-749, Korea.
authors.forename: Sangdun
authors.initials: S
authors.lastname: Choi
mesh_terms: D051700:Activating Transcription Factor 3 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D056284:Histone Deacetylase 1 / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D011485:Protein Binding; D021381:Protein Transport; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000378:metabolism*
chemical_list: D051700:Activating Transcription Factor 3; D008070:Lipopolysaccharides; D051996:Transcription Factor RelA; D056284:Histone Deacetylase 1