NFκB regulates expression of Polo-like kinase 4

Adeline C. Ledoux; Hélène Sellier; Katie Gillies; Alessio Iannetti; John James; Neil D. Perkins

doi:10.4161/cc.26086

NFκB regulates expression of Polo-like kinase 4

Adeline C. Ledoux
, Hélène Sellier
, Katie Gillies
, Alessio Iannetti
, John James
, Neil D. Perkins^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

28 Citations (Scopus)

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 (PLκ4) is a direct NFκB target gene. RNA interference, chromatin immunoprecipitation, and analysis of the PLκ4 promoter in a luciferase reporter assay revealed that all NFκB subunits participate in its regulation. Moreover, we demonstrate that NFκB regulation of PLκ4 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 NF κB activity in cancer can lead to increased genomic instability and uncontrolled proliferation.

Original language	English
Pages (from-to)	3052-3062
Number of pages	11
Journal	Cell Cycle
Volume	12
Issue number	18
DOIs	https://doi.org/10.4161/cc.26086
Publication status	Published - 15 Sept 2013

Bibliographical note

Funding Information:
We would like to thank Mónica Bettencourt Dias and members of the NDP lab for helpful comments. ACL was funded by a Cancer Research UK PhD studentship (C1443/A9215), HS is funded by the Wellcome Trust (grant 094,409) and AI is funded by the European Union FP7 “Inflacare” consortium. Additional NDP Lab funding was received from Cancer Research UK program grant C1443/A12750.

Funding

We would like to thank Mónica Bettencourt Dias and members of the NDP lab for helpful comments. ACL was funded by a Cancer Research UK PhD studentship (C1443/A9215), HS is funded by the Wellcome Trust (grant 094,409) and AI is funded by the European Union FP7 “Inflacare” consortium. Additional NDP Lab funding was received from Cancer Research UK program grant C1443/A12750.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Cancer
Cell cycle
Centrosome
IKK
Mitosis
NFκB
PLK4
Promoter

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10.4161/cc.26086

Cite this

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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 (PLκ4) is a direct NFκB target gene. RNA interference, chromatin immunoprecipitation, and analysis of the PLκ4 promoter in a luciferase reporter assay revealed that all NFκB subunits participate in its regulation. Moreover, we demonstrate that NFκB regulation of PLκ4 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 NF κB activity in cancer can lead to increased genomic instability and uncontrolled proliferation.",

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author = "Ledoux, \{Adeline C.\} and H{\'e}l{\`e}ne Sellier and Katie Gillies and Alessio Iannetti and John James and Perkins, \{Neil D.\}",

note = "Funding Information: We would like to thank M{\'o}nica Bettencourt Dias and members of the NDP lab for helpful comments. ACL was funded by a Cancer Research UK PhD studentship (C1443/A9215), HS is funded by the Wellcome Trust (grant 094,409) and AI is funded by the European Union FP7 “Inflacare” consortium. Additional NDP Lab funding was received from Cancer Research UK program grant C1443/A12750.",

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doi = "10.4161/cc.26086",

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AU - Sellier, Hélène

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AU - Iannetti, Alessio

AU - James, John

AU - Perkins, Neil D.

N1 - Funding Information: We would like to thank Mónica Bettencourt Dias and members of the NDP lab for helpful comments. ACL was funded by a Cancer Research UK PhD studentship (C1443/A9215), HS is funded by the Wellcome Trust (grant 094,409) and AI is funded by the European Union FP7 “Inflacare” consortium. Additional NDP Lab funding was received from Cancer Research UK program grant C1443/A12750.

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N2 - 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 (PLκ4) is a direct NFκB target gene. RNA interference, chromatin immunoprecipitation, and analysis of the PLκ4 promoter in a luciferase reporter assay revealed that all NFκB subunits participate in its regulation. Moreover, we demonstrate that NFκB regulation of PLκ4 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 NF κB activity in cancer can lead to increased genomic instability and uncontrolled proliferation.

AB - 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 (PLκ4) is a direct NFκB target gene. RNA interference, chromatin immunoprecipitation, and analysis of the PLκ4 promoter in a luciferase reporter assay revealed that all NFκB subunits participate in its regulation. Moreover, we demonstrate that NFκB regulation of PLκ4 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 NF κB activity in cancer can lead to increased genomic instability and uncontrolled proliferation.

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KW - Cell cycle

KW - Centrosome

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KW - Mitosis

KW - NFκB

KW - PLK4

KW - Promoter

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ER -

NFκB regulates expression of Polo-like kinase 4

Abstract

Bibliographical note

Funding

UN SDGs

Keywords

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