p53-dependent transcriptional suppression of BAG3 protects cells against metabolic stress via facilitation of p53 accumulation
p53-dependent transcriptional suppression of BAG3 protects cells against metabolic stress via facilitation of p53 accumulation
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BAG3 的 p53 依赖性转录抑制通过促进 p53 积累来保护细胞免受代谢应激
DOI：
10.1111/jcmm.14764
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发表时间：
2019
影响因子：
5.3
通讯作者：
Wang Hua Qin
中科院分区：
文献类型：
--
作者：
Wang Jia Mei;Liu Bao Qin;Du Zhen Xian;Li Chao;Sun Jia;Yan Jing;Jiang Jing Yi;Wang Hua Qin
实体瘤在肿瘤发展过程中，由于血液供应不足和高营养消耗，经常发生代谢应激。P53被葡萄糖限制激活，通过触发代谢检查点维持细胞存活。然而，确切的下游贡献者并没有完全确定。BAG3是一种具有多种细胞功能的辅伴侣，与胰腺癌细胞的代谢重编程有关。目前的研究表明，葡萄糖限制以p53依赖的方式转录抑制BAG3的表达。重要的是，其下调受阻会损害细胞对葡萄糖不足引发的代谢应激的适应，支持BAG3可能是p53细胞适应代谢应激的下游贡献者之一。我们的数据显示，代谢应激下，异位BAG3表达通过直接相互作用抑制p53的积累。因此，本研究强调了p53介导的BAG3抑制通过促进p53积累在细胞适应代谢应激中的重要性。
Solid tumour frequently undergoes metabolic stress during tumour development because of inadequate blood supply and the high nutrient expenditure. p53 is activated by glucose limitation and maintains cell survival via triggering metabolic checkpoint. However, the exact downstream contributors are not completely identified. BAG3 is a cochaperone with multiple cellular functions and is implicated in metabolic reprogramming of pancreatic cancer cells. The current study demonstrated that glucose limitation transcriptionally suppressed BAG3 expression in a p53‐dependent manner. Importantly, hinderance of its down‐regulation compromised cellular adaptation to metabolic stress triggered by glucose insufficiency, supporting that BAG3 might be one of p53 downstream contributors for cellular adaptation to metabolic stress. Our data showed that ectopic BAG3 expression suppressed p53 accumulation via direct interaction under metabolic stress. Thereby, the current study highlights the significance of p53‐mediated BAG3 suppression in cellular adaptation to metabolic stress via facilitating p53 accumulation.