Efficient DNA binding of NF-κB requires the chaperone-like function of NPM1

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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.

Journal

  • Nucleic acids research

    Nucleic acids research 45(7), 3707-3723, 2016-12

    Oxford University Press

Keywords

Codes

  • NII Article ID (NAID)
    120006223991
  • NII NACSIS-CAT ID (NCID)
    AA00760269
  • Text Lang
    ENG
  • Article Type
    journal article
  • ISSN
    0305-1048
  • Data Source
    IR 
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