Sestrin 2 protects against metabolic stress in a p53-independent manner.
Sestrin 2 protects against metabolic stress in a p53-independent manner.
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DOI：
10.1016/j.bbrc.2019.04.072
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发表时间：
2019-06
影响因子：
3.1
通讯作者：
Jia-Mei Wang;Bao-qin Liu;Chao Li;Zhen‐Xian Du;Jia Sun;Jing Yan;Jing-Yi Jiang;Hua-Qin Wang
中科院分区：
文献类型：
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作者：
Jia-Mei Wang;Bao-qin Liu;Chao Li;Zhen‐Xian Du;Jia Sun;Jing Yan;Jing-Yi Jiang;Hua-Qin Wang
葡萄糖限制激活p53，其功能是维持细胞存活的适应性反应。然而，p53在多种肿瘤中经常缺失或突变，而大多数癌细胞可以适应代谢不利的环境，这表明p53缺失或突变的癌细胞对代谢不利环境的适应性反应存在p53反激活以外的其他机制。Sestrin 2 （SESN2）是p53的下游靶点，对多种应激刺激（如基因毒性、能量和氧化应激）起保护作用。在目前的研究中，我们证明了无论p53状态如何，葡萄糖限制在转录后水平都能稳定SESN2转录本。重要的是，SESN2还以不依赖p53的方式保护细胞免受葡萄糖限制引发的代谢应激。我们的数据表明，SESN2转录物的稳定可能是除了p53激活之外对代谢应激的另一种适应性反应。因此，本研究强调了SESN2转录物稳定在p53缺失或突变细胞适应代谢应激中的重要意义。
Glucose limitation activates p53, which functions as an adaptive response to maintain cell survival. However, p53 is frequently deleted or mutated in a variety of tumors, while most cancer cells can acclimatize themselves to metabolically unfavorable surrounding, indicating that alternative mechanisms other than p53 transactivation underly adaptive response of cancer cells with p53 deletion or mutation to metabolically hostile environment. Sestrin 2 (SESN2) is a p53 downstream target, which plays a protective role against various stressful stimuli, such as genotoxic, energetic, and oxidative stress. In the current study, we demonstrated that SESN2 transcript was stabilized by glucose limitation at the posttranscriptional level irrespective of p53 status. Importantly, SESN2 also protected cells from metabolic stress triggered by glucose limitation in a p53-independent manner. Our data indicated that stabilization of SESN2 transcript might be an alternative adaptive response to metabolic stress other than p53 activation. Thereby, the current study highlights the significance of stabilization of SESN2 transcript in adaptation of cells with p53 deletion or mutation to metabolic stress.