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Open AccessFeature PaperReview

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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Author to whom correspondence should be addressed.
Cells 2018, 7(10), 157; https://doi.org/10.3390/cells7100157
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)
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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MDPI and ACS Style

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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