P53-regulated autophagy and its impact on drug resistance and cell fate.
P53-regulated autophagy and its impact on drug resistance and cell fate.
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DOI：
10.20517/cdr.2020.85
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Maki CG
中科院分区：
文献类型：
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作者：
Shim D;Duan L;Maki CG
野生型p53是一种应激反应性转录因子，也是一种有效的肿瘤抑制因子。P53通过阻断其增殖或通过凋亡诱导其死亡来抑制初期癌细胞的生长。自噬是一种自我吞噬的过程，在应对压力中起着关键作用。在自噬过程中，细胞器和其他细胞内成分在自噬溶酶体中降解，自噬分解产物再循环进入生存所需的代谢和能量产生途径。P53可以促进或抑制自噬，这取决于其亚细胞定位、突变状态和应激水平。在几项研究中已经报道了阻断自噬以增加p53介导的细胞凋亡，揭示了自噬可以响应于活化的p53而影响细胞命运，并且是增加p53依赖性肿瘤抑制的潜在靶点。
Wild-type p53 is a stress-responsive transcription factor and a potent tumor suppressor. P53 inhibits the growth of incipient cancer cells by blocking their proliferation or inducing their death through apoptosis. Autophagy is a self-eating process that plays a key role in response to stress. During autophagy, organelles and other intracellular components are degraded in autophagolysosomes and the autophagic breakdown products are recycled into metabolic and energy producing pathways needed for survival. P53 can promote or inhibit autophagy depending on its subcellular localization, mutation status, and the level of stress. Blocking autophagy has been reported in several studies to increase p53-mediated apoptosis, revealing that autophagy can influence cell-fate in response to activated p53 and is a potential target to increase p53-dependent tumor suppression.