| First Author | Lin J | Year | 2017 |
| Journal | Nucleic Acids Res | Volume | 45 |
| Issue | 7 | Pages | 3707-3723 |
| PubMed ID | 28003476 | Mgi Jnum | J:246286 |
| Mgi Id | MGI:5923001 | Doi | 10.1093/nar/gkw1285 |
| Citation | Lin J, et al. (2017) Efficient DNA binding of NF-kappaB requires the chaperone-like function of NPM1. Nucleic Acids Res 45(7):3707-3723 |
| abstractText | 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-kappaB (NF-kappaB), a master regulator of inflammation. We found that NPM1 knockdown decreased NF-kappaB-mediated transcription of selected target genes by decreasing the recruitment of NF-kappaB 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-kappaB complex. This result suggests that NF-kappaB 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-alpha) and lipopolysaccharide in fibroblasts and macrophages. The NF-kappaB-mediated invasion of breast cancer cells was significantly decreased by NPM1 knockdown. Our study suggests a novel mechanistic insight into the NF-kappaB-mediated transcription and an oncogenic role of NPM1 in both tumor cells and the tumor micro-environment through the regulation of NF-kappaB. |
