Insights into the Relationship between Nucleolar Stress and the NF-kappa B Pathway

The nuclear organelle the nucleolus and the transcription factor nuclear factor of kappa-light-chain-enhancer of activated B cells (NF-kappa B) are both central to the control of cellular homeostasis, dysregulated in common diseases and implicated in the ageing process. Until recently, it was believed that they acted independently to regulate homeostasis in health and disease. However, there is an emerging body of evidence suggesting that nucleoli and NF-kappa B signalling converge at multiple levels. Here we will review current understanding of this crosstalk. We will discuss activation of the NF-kappa B pathway by nucleolar stress and induction of apoptosis by nucleolar sequestration of NF-kappa B/RelA. We will also discuss the role of TIF-IA, COMMD1, and nucleophosmin, which are key players in this crosstalk, and the therapeutic relevance, particularly with respect to the antitumour effects of aspirin.