Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

NF-kB Nucleoli Crosstalk in Stress Response and the Regulation of Apoptosis

Version 1 : Received: 4 September 2018 / Approved: 4 September 2018 / Online: 4 September 2018 (04:49:10 CEST)

A peer-reviewed article of this Preprint also exists.

Chen, J.; Stark, L.A. Crosstalk between NF-κB and Nucleoli in the Regulation of Cellular Homeostasis. Cells 2018, 7, 157. Chen, J.; Stark, L.A. Crosstalk between NF-κB and Nucleoli in the Regulation of Cellular Homeostasis. Cells 2018, 7, 157.


Nucleoli are emerging as key sensors of cellular stress and regulators of the downstream consequences on proliferation, metabolism, senescence and apoptosis. NF-kB signalling is activated in response to a similar plethora of stresses, which leads to modulation of cell growth and death programs. Although these 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 IkB degradation and NF-kB nuclear translocation. Under these stress conditions, the RelA component of NF-kB 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 the anti-tumour mechanism of aspirin and small molecule CDK4 inhibitors. We will also briefly discuss how NF-kB-nucleoli crosstalk may be more broadly relevant to the regulation of cellular homeostasis and how it may be exploited for therapeutic purpose.


nucleolus; RRN3; I-kappaB; stress; aspirin; CDK4; RelA; p65; cancer; neurodegenerative disorders


Biology and Life Sciences, Biochemistry and Molecular Biology

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