ATF3 promotes erastin-induced ferroptosis by suppressing system Xc-

被引：649

作者：

Wang, Liyuan ^{[1
,2
]}

Liu, Yichen ^{[3
]}

Du, Tingting ^{[1
,2
]}

Yang, Heng ^{[2
]}

Lei, Lei ^{[4
]}

Guo, Mengqi ^{[4
]}

Ding, Han-Fei ^{[2
,5
]}

Zhang, Junran ^{[6
]}

Wang, Hongbo ^{[4
]}

Chen, Xiaoguang ^{[1
]}

Yan, Chunhong ^{[2
,7
]}

机构：

[1] Chinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, Beijing, Peoples R China

[2] Augusta Univ, Georgia Canc Ctr, Augusta, GA USA

[3] Harbin Commercial Univ, Harbin, Heilongjiang, Peoples R China

[4] Yantai Univ, Sch Pharm, Yantai, Shandong, Peoples R China

[5] Augusta Univ, Med Coll Georgia, Dept Pathol, Augusta, GA USA

[6] Ohio State Univ, Dept Radiat Oncol, Columbus, OH 43210 USA

[7] Augusta Univ, Dept Biochem & Mol, Med Coll Georgia, Augusta, GA USA

来源：

CELL DEATH AND DIFFERENTIATION | 2020年 / 27卷 / 02期

关键词：

ACTIVATING TRANSCRIPTION FACTOR-3; CELL-DEATH; CYSTINE/GLUTAMATE ANTIPORTER; CANCER-CELLS; RESPONSE GENE; EXPRESSION; P53; INDUCTION; ROLES; ANGIOGENESIS;

D O I：

10.1038/s41418-019-0380-z

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 amino acid antiporter system Xc(-) is important for the synthesis of glutathione (GSH) that functions to prevent lipid peroxidation and protect cells from nonapoptotic, iron-dependent death (i.e., ferroptosis). While the activity of system Xc(-) often positively correlates with the expression level of its light chain encoded by SLC7A11, inhibition of system Xc(-) activity by small molecules (e.g., erastin) causes a decrease in the intracellular GSH level, leading to ferroptotic cell death. How system Xc(-) is regulated during ferroptosis remains largely unknown. Here we report that activating transcription factor 3 (ATF3), a common stress sensor, can promote ferroptosis induced by erastin. ATF3 suppressed system Xc(-), depleted intracellular GSH, and thereby promoted lipid peroxidation induced by erastin. ATF3 achieved this activity through binding to the SLC7A11 promoter and repressing SLC7A11 expression in a p53-independent manner. These findings thus add ATF3 to a short list of proteins that can regulate system Xc(-) and promote ferroptosis repressed by this antiporter.

引用

页码：662 / 675

页数：14

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