NF kappa B regulates expression of Polo-like kinase 4

作者：Ledoux Adeline C; Sellier Helene; Gillies Katie; Iannetti Alessio; James John; Perkins Neil D^*

来源：Cell Cycle, 2013, 12(18): 3052-3062.

DOI：10.4161/cc.26086

• NF kappa B
• PLK4
• centrosome
• mitosis
• promoter
• cell cycle
• cancer
• IKK

Activation of the NF kappa B signaling pathway allows the cell to respond to infection and stress and can affect many cellular processes. As a consequence, NF kappa B activity must be integrated with a wide variety of parallel signaling pathways. One mechanism through which NF kappa B can exert widespread effects is through controlling the expression of key regulatory kinases. Here we report that NF kappa B regulates the expression of genes required for centrosome duplication, and that Polo-like kinase 4 (PLK4) is a direct NF kappa B target gene. RNA interference, chromatin immunoprecipitation, and analysis of the PLK4 promoter in a luciferase reporter assay revealed that all NF kappa B subunits participate in its regulation. Moreover, we demonstrate that NF kappa B regulation of PLK4 expression is seen in multiple cell types. Significantly long-term deletion of the NF kappa B2 (p100/p52) subunit leads to defects in centrosome structure. This data reveals a new component of cell cycle regulation by NF kappa B and suggests a mechanism through which deregulated NF kappa B activity in cancer can lead to increased genomic instability and uncontrolled proliferation.

• 出版日期2013-9-15