Thoms Hazel C, Stark Lesley A
The Stark Lab, Edinburgh Cancer Research Centre, Institute of Genetics and Cancer, University of Edinburgh, Crewe Rd. South, Edinburgh EH4 2XU, UK.
Biomedicines. 2021 Aug 25;9(9):1082. doi: 10.3390/biomedicines9091082.
The nuclear organelle, the nucleolus, plays a critical role in stress response and the regulation of cellular homeostasis. P53 as a downstream effector of nucleolar stress is well defined. However, new data suggests that NF-κB also acts downstream of nucleolar stress to regulate cell growth and death. In this review, we will provide insight into the NF-κB nucleolar stress response pathway. We will discuss apoptosis mediated by nucleolar sequestration of RelA and new data demonstrating a role for p62 (sequestosome () in this process. We will also discuss activation of NF-κB signalling by degradation of the RNA polymerase I (PolI) complex component, transcription initiation factor-IA (TIF-IA ()), and contexts where TIF-IA-NF-κB signalling may be important. Finally, we will discuss how this pathway is targeted by aspirin to mediate apoptosis of colon cancer cells.
核细胞器核仁在应激反应和细胞稳态调节中发挥着关键作用。p53作为核仁应激的下游效应因子已被明确。然而，新数据表明NF-κB也在核仁应激下游发挥作用，以调节细胞生长和死亡。在本综述中，我们将深入探讨NF-κB核仁应激反应途径。我们将讨论RelA在核仁中隔离介导的细胞凋亡以及新数据证明p62（聚集体蛋白）在此过程中的作用。我们还将讨论RNA聚合酶I（PolI）复合物成分转录起始因子-IA（TIF-IA）降解导致的NF-κB信号激活，以及TIF-IA-NF-κB信号可能重要的背景。最后，我们将讨论这条途径如何被阿司匹林靶向，以介导结肠癌细胞的凋亡。
