The p53-inducible long noncoding RNA TRINGS protects cancer cells from necrosis under glucose starvation

被引:74
作者
Khan, Muhammad Riaz [1 ]
Xiang, Shaoxun [1 ]
Song, Zhiyin [2 ]
Wu, Mian [1 ,3 ]
机构
[1] Univ Sci & Technol China, CAS Key Lab Innate Immun & Chron Dis, CAS Ctr Excellence Cell & Mol Biol, Innovat Ctr Cell Signaling Network,Sch Life Sci, Hefei, Anhui, Peoples R China
[2] Wuhan Univ, Coll Life Sci, Hubei Key Lab Cell Homeostasis, Wuhan, Hubei, Peoples R China
[3] Henan Univ, Translat Res Inst, Sch Med, Henan Prov Peoples Hosp, Zhengzhou, Henan, Peoples R China
基金
国家重点研发计划; 中国国家自然科学基金;
关键词
glucose starvation; necroptosis; p53; STRAP; TRINGS; P53; STRAP; PHOSPHORYLATION; INHIBITION; APOPTOSIS; DEATH; BETA; TRANSCRIPTION; EXPRESSION; KINASE-3;
D O I
10.15252/embj.201696239
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The tumor suppressor p53 is activated in response to cellular stress to prevent malignant transformation. However, several recent studies have shown that p53 can play protective roles in tumor cell survival under adversity. Whether p53-regulated long noncoding RNAs are involved in this process remains to be fully understood. Here, we show that under glucose starvation condition, p53 directly upregulates a novel lncRNA named TRINGS (Tp53-regulated inhibitor of necrosis under glucose starvation) in human tumor cells. TRINGS binds to STRAP and inhibits STRAP-GSK3 beta-NF-kappa B necrotic signaling to protect tumor cells from cell death. Interestingly, TRINGS appears to respond to glucose starvation specifically, as it is not activated by serum, serine, or glutamine deprivation. Collectively, our findings reveal that p53-induced lncRNA TRINGS controls the necrotic pathway and contributes to the survival of cancer cells harboring wild-type p53 under glucose stress.
引用
收藏
页码:3483 / 3500
页数:18
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