ATF3 promotes erastin-induced ferroptosis by suppressing system Xc.
Cell Death Differ
; 27(2): 662-675, 2020 02.
Article
in En
| MEDLINE
| ID: mdl-31273299
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Piperazines
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Amino Acid Transport System y/
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Activating Transcription Factor 3
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Ferroptosis
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Antineoplastic Agents
Limits:
Humans
Language:
En
Journal:
Cell Death Differ
Year:
2020
Document type:
Article
Affiliation country:
China