title: NFκB regulates expression of Polo-like kinase 4.
abstract: Activation of the NFκB signaling pathway allows the cell to respond to infection and stress and can affect many cellular processes. As a consequence, NFκB activity must be integrated with a wide variety of parallel signaling pathways. One mechanism through which NFκB can exert widespread effects is through controlling the expression of key regulatory kinases. Here we report that NFκB regulates the expression of genes required for centrosome duplication, and that Polo-like kinase 4 (PLK4) is a direct NFκB target gene. RNA interference, chromatin immunoprecipitation, and analysis of the PLK4 promoter in a luciferase reporter assay revealed that all NFκB subunits participate in its regulation. Moreover, we demonstrate that NFκB regulation of PLK4 expression is seen in multiple cell types. Significantly long-term deletion of the NFκB2 (p100/p52) subunit leads to defects in centrosome structure. This data reveals a new component of cell cycle regulation by NFκB and suggests a mechanism through which deregulated NFκB activity in cancer can lead to increased genomic instability and uncontrolled proliferation.
authors: Institute for Cell and Molecular Biosciences; Faculty of Medical Sciences; Newcastle University; Newcastle Upon Tyne, UK.
authors: Adeline C
authors: AC
authors: Ledoux
authors: Hélène
authors: H
authors: Sellier
authors: Katie
authors: K
authors: Gillies
authors: Alessio
authors: A
authors: Iannetti
authors: John
authors: J
authors: James
authors: Neil D
authors: ND
authors: Perkins
mesh_terms: D045744:Cell Line, Tumor; D018385:Centrosome / Q000737:chemistry / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D042822:Genomic Instability; D006367:HeLa Cells; D006801:Humans; D052003:NF-kappa B p52 Subunit / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D052003:NF-kappa B p52 Subunit; C498206:NFKB2 protein, human; D034741:RNA, Small Interfering; C490219:PLK4 protein, human; D017346:Protein Serine-Threonine Kinases
keywords: IKK; NFκB; PLK4; cancer; cell cycle; centrosome; mitosis; promoter
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