Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P05412 (
c-Jun
)
11,453
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Ferroptosis is a metabolism-related cell death. Stimulating ferroptosis in liver cancer cells is a strategy to treat liver cancer. However, how to eradicate liver cancer cells through ferroptosis and the obstacles to inducing ferroptosis in liver cancer remain unclear. Here, we observed that erastin suppressed the malignant phenotypes of liver cancer cells by inhibiting O-GlcNAcylation of
c-Jun
and further inhibited protein expression, transcription activity and nuclear accumulation of
c-Jun
. Overexpression of
c-Jun
-WT with simultaneous PuGNAc treatment conversely inhibited erastin-induced ferroptosis, whereas overexpression of
c-Jun
-WT alone or overexpression of
c-Jun
-S73A (a non-O-GlcNAcylated form of
c-Jun
) with PuGNAc treatment did not exert a similar effect. GSH downregulation induced by erastin was restored by overexpression of
c-Jun
-WT with simultaneous PuGNAc treatment. In addition, overexpression of
c-Jun
-WT, but not its S73A mutant, induced
PSAT1
and CBS transcription via directly binding to their promoter regions, suggesting that GSH synthesis is regulated by O-GlcNAcylated
c-Jun
. A positive correlation between
c-Jun
O-GlcNAcylation and GSH was observed in clinical samples. Collectively, O-GlcNAcylated
c-Jun
represents an obstructive factor to ferroptosis, and targeting O-GlcNAcylated
c-Jun
might be helpful for treating liver cancer.
...
PMID:O-GlcNAcylated c-Jun antagonizes ferroptosis via inhibiting GSH synthesis in liver cancer. 3139 93
