Nucleolus and Nucleolar Stress: From Cell Fate Decision to Disease Development.
Nucleolus and Nucleolar Stress: From Cell Fate Decision to Disease Development.
复制标题
核仁和核仁应激：从细胞命运决定到疾病发展
作者：
除了核糖体生物发生中的典型功能外，最近在核仁在应激反应、细胞命运决定和疾病进展中的迷人作用方面也取得了重大进展。核仁应激是一个新出现的概念，描述了在应激条件下核仁合成和核糖体生物发生受损所导致的核仁结构和功能的异常，已与多种信号转导联系在一起，包括但不限于MDM2-P53、NF-κB和HIF-1α通路。研究发现，当细胞遇到各种应激条件，如营养缺乏、DNA损伤以及氧化和热应激时，核仁是应激传感器和信号中枢。因此，核仁应激在决定细胞命运中起着关键作用，如细胞凋亡、衰老、自噬和分化，以响应应激诱导的损伤。核仁稳态参与了多种慢性疾病的发病机制，特别是肿瘤发生、神经退行性疾病和代谢紊乱。机械论的洞察力揭示了核仁启动的信号在这些疾病的进展中不可或缺的作用。因此，核仁应激的干预可能为开发针对这些疾病的新疗法铺平道路。本文系统地总结了核仁与应激反应、信号转导和细胞命运决定的关系，重点阐述了核仁应激驱动疾病进展的机制，并强调了介入核仁在疾病治疗中的优点。
Besides the canonical function in ribosome biogenesis, there have been significant recent advances towards the fascinating roles of the nucleolus in stress response, cell destiny decision and disease progression. Nucleolar stress, an emerging concept describing aberrant nucleolar structure and function as a result of impaired rRNA synthesis and ribosome biogenesis under stress conditions, has been linked to a variety of signaling transductions, including but not limited to Mdm2-p53, NF-κB and HIF-1α pathways. Studies have uncovered that nucleolus is a stress sensor and signaling hub when cells encounter various stress conditions, such as nutrient deprivation, DNA damage and oxidative and thermal stress. Consequently, nucleolar stress plays a pivotal role in the determination of cell fate, such as apoptosis, senescence, autophagy and differentiation, in response to stress-induced damage. Nucleolar homeostasis has been involved in the pathogenesis of various chronic diseases, particularly tumorigenesis, neurodegenerative diseases and metabolic disorders. Mechanistic insights have revealed the indispensable role of nucleolus-initiated signaling in the progression of these diseases. Accordingly, the intervention of nucleolar stress may pave the path for developing novel therapies against these diseases. In this review, we systemically summarize recent findings linking the nucleolus to stress responses, signaling transduction and cell-fate decision, set the spotlight on the mechanisms by which nucleolar stress drives disease progression, and highlight the merit of the intervening nucleolus in disease treatment.
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影响因子：
7.8
作者：
Smith DL Jr;Li C;Matecic M;Maqani N;Bryk M;Smith JS
通讯作者：
Smith JS
影响因子：
7.1
作者：
Aladesuyi Arogundade O;Nguyen S;Leung R;Wainio D;Rodriguez M;Ravits J
通讯作者：
Ravits J
影响因子：
14.9
作者：
Chen J;Lobb IT;Morin P;Novo SM;Simpson J;Kennerknecht K;von Kriegsheim A;Batchelor EE;Oakley F;Stark LA
通讯作者：
Stark LA
影响因子：
21.3
作者：
Colombo, E;Marine, JC;Pelicci, PG
通讯作者：
Pelicci, PG
影响因子：
7.7
作者：
Bianco, Christopher;Mohr, Ian
通讯作者：
Mohr, Ian