Open Accessp53‐dependent transcriptional suppression of BAG3 protects cells against metabolic stress via facilitation of p53 accumulation
Author(s) -
Wang JiaMei,
Liu BaoQin,
Du ZhenXian,
Li Chao,
Sun Jia,
Yan Jing,
Jiang JingYi,
Wang HuaQin
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.14764
Subject(s) - bag3 , microbiology and biotechnology , biology , downregulation and upregulation , cellular adaptation , cellular stress response , reprogramming , transcriptome , cancer research , cell , autophagy , fight or flight response , gene expression , gene , biochemistry , apoptosis
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.