Efficient DNA binding of NF-?B 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-?B (NF-?B), a master regulator of inflammation. We found that NPM1 knockdown decreased NF-?B-mediated transcription of selected target genes by decreasing the recruitment of NF-?B 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-?B complex. This result suggests that NF-?B 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-?) and lipopolysaccharide in fibroblasts and macrophages. The NF-?B-mediated invasion of breast cancer cells was significantly decreased by NPM1 knockdown. Our study suggests a novel mechanistic insight into the NF-?B-mediated transcription and an oncogenic role of NPM1 in both tumor cells and the tumor micro-environment through the regulation of NF-?B.

SUBMITTER: Lin J 

PROVIDER: S-EPMC5397172 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature