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 fibrobla

SUBMITTER: Lin J 

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

REPOSITORIES: biostudies-literature