Journal
CELL CYCLE
Volume 12, Issue 18, Pages 3052-3062Publisher
LANDES BIOSCIENCE
DOI: 10.4161/cc.26086
Keywords
NF kappa B; PLK4; centrosome; mitosis; promoter; cell cycle; cancer; IKK
Categories
Funding
- Cancer Research UK PhD studentship [C1443/A9215]
- Wellcome Trust [094,409]
- European Union
- Cancer Research UK [C1443/A12750]
- Worldwide Cancer Research [13-1150] Funding Source: researchfish
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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.
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