title: Efficient DNA binding of NF-κB requires the chaperone-like function of NPM1.
abstract: NPM1/nucleophosmin is frequently overexpressed in various tumors, although the oncogenic role of NPM1 remains unclear. Here we revealed the link between NPM1 and nuclear factor-κB (NF-κB), a master regulator of inflammation. We found that NPM1 knockdown decreased NF-κB-mediated transcription of selected target genes by decreasing the recruitment of NF-κB p65 to the gene promoters. NPM1 is directly associated with the DNA binding domain of p65 to enhance its DNA binding activity without being a part of the DNA-NF-κB complex. This result suggests that NF-κB requires the chaperone-like function of NPM1 for DNA binding. Furthermore, we demonstrated that NPM1 was required for efficient inflammatory gene expression induced by tumor necrosis factor alpha (TNF-α) and lipopolysaccharide in fibroblasts and macrophages. The NF-κB-mediated invasion of breast cancer cells was significantly decreased by NPM1 knockdown. Our study suggests a novel mechanistic insight into the NF-κB-mediated transcription and an oncogenic role of NPM1 in both tumor cells and the tumor micro-environment through the regulation of NF-κB.
authors.affiliation: PhD Program in Human Biology, School of Integrative and Global Majors, University of Tsukuba, 1-1-1, Tennodai, Tsukuba 305-8575 Japan.|Department of Infection Biology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba 305-8575 Japan.
authors.forename: Jianhuang
authors.initials: J
authors.lastname: Lin
authors.affiliation: PhD Program in Human Biology, School of Integrative and Global Majors, University of Tsukuba, 1-1-1, Tennodai, Tsukuba 305-8575 Japan.|Department of Experimental Pathology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba 305-8575 Japan.
authors.forename: Mitsuyasu
authors.initials: M
authors.lastname: Kato
authors.affiliation: Department of Infection Biology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba 305-8575 Japan.
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Nagata
authors.affiliation: PhD Program in Human Biology, School of Integrative and Global Majors, University of Tsukuba, 1-1-1, Tennodai, Tsukuba 305-8575 Japan.|Department of Infection Biology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba 305-8575 Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Okuwaki
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism* / Q000502:physiology; D000090243:Nucleophosmin; D011485:Protein Binding; D051996:Transcription Factor RelA / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D016328:NF-kappa B; C000716967:NPM1 protein, human; C000715570:Npm1 protein, mouse; D009687:Nuclear Proteins; D051996:Transcription Factor RelA; D000090243:Nucleophosmin; D004247:DNA