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Cells 2018, 7(10), 157; https://doi.org/10.3390/cells7100157

Crosstalk between NF-κB and Nucleoli in the Regulation of Cellular Homeostasis

Edinburgh Cancer Research Centre, Institute of Genetics and Molecular Medicine (IGMM) University of Edinburgh; Edinburgh EH42XU, Scotland, UK
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Received: 4 September 2018 / Revised: 28 September 2018 / Accepted: 3 October 2018 / Published: 5 October 2018
(This article belongs to the Special Issue NF-κB in Cancer)
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Abstract

Nucleoli are emerging as key sensors of cellular stress and regulators of the downstream consequences on proliferation, metabolism, senescence, and apoptosis. NF-κB signalling is activated in response to a similar plethora of stresses, which leads to modulation of cell growth and death programs. While nucleolar and NF-κB pathways are distinct, it is increasingly apparent that they converge at multiple levels. Exposure of cells to certain insults causes a specific type of nucleolar stress that is characterised by degradation of the PolI complex component, TIF-IA, and increased nucleolar size. Recent studies have shown that this atypical nucleolar stress lies upstream of cytosolic IκB degradation and NF-κB nuclear translocation. Under these stress conditions, the RelA component of NF-κB accumulates within functionally altered nucleoli to trigger a nucleophosmin dependent, apoptotic pathway. In this review, we will discuss these points of crosstalk and their relevance to anti-tumour mechanism of aspirin and small molecule CDK4 inhibitors. We will also briefly the discuss how crosstalk between nucleoli and NF-κB signalling may be more broadly relevant to the regulation of cellular homeostasis and how it may be exploited for therapeutic purpose. View Full-Text
Keywords: Nucleolus; TIF-IA(RRN3); I-kappaB; stress; aspirin; CDK4; RelA; p65; cancer; neurodegenerative disorders; NF-κB; non-steroidal anti-inflammatory drugs (NSAIDs) Nucleolus; TIF-IA(RRN3); I-kappaB; stress; aspirin; CDK4; RelA; p65; cancer; neurodegenerative disorders; NF-κB; non-steroidal anti-inflammatory drugs (NSAIDs)
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Chen, J.; Stark, L.A. Crosstalk between NF-κB and Nucleoli in the Regulation of Cellular Homeostasis. Cells 2018, 7, 157.

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