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NF kappa B regulates expression of Polo-like kinase 4

Lookup NU author(s): Dr Adeline Ledoux, Helene Sellier, Dr Alessio Iannetti, Professor Neil PerkinsORCiD

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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).


Abstract

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.


Publication metadata

Author(s): Ledoux AC, Sellier H, Gillies K, Iannetti A, James J, Perkins ND

Publication type: Article

Publication status: Published

Journal: Cell Cycle

Year: 2013

Volume: 12

Issue: 18

Pages: 3052-3062

Print publication date: 21/08/2013

Date deposited: 07/07/2015

ISSN (print): 1538-4101

ISSN (electronic): 1551-4005

Publisher: Landes Bioscience

URL: http://dx.doi.org/10.4161/cc.26086

DOI: 10.4161/cc.26086


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Funding

Funder referenceFunder name
European Union
094,409Wellcome Trust
C1443/A12750Cancer Research UK
C1443/A9215Cancer Research UK PhD studentship
94409

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