学術雑誌論文 Efficient DNA binding of NF-κB requires the chaperone-like function of NPM1

Lin, Jianhuang  ,  Kato, Mitsuyasu  ,  Nagata, Kyosuke  ,  Okuwaki, Mitsuru

45 ( 7 )  , pp.3707 - 3723 , 2016-12 , Oxford University Press
ISSN:0305-1048
NII書誌ID(NCID):AA00760269
内容記述
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.
本文を読む

https://tsukuba.repo.nii.ac.jp/?action=repository_action_common_download&item_id=41104&item_no=1&attribute_id=17&file_no=1

このアイテムのアクセス数:  回

その他の情報