Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10189)
Regulator Name Forkhead box protein O4 (FOXO4)
Synonyms
AFX, AFX1, MLLT7; Fork head domain transcription factor AFX1
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Gene Name FOXO4
Gene ID 4303
Regulator Type Protein coding
Uniprot ID P98177
Sequence
MDPGNENSATEAAAIIDLDPDFEPQSRPRSCTWPLPRPEIANQPSEPPEVEPDLGEKVHT
EGRSEPILLPSRLPEPAGGPQPGILGAVTGPRKGGSRRNAWGNQSYAELISQAIESAPEK
RLTLAQIYEWMVRTVPYFKDKGDSNSSAGWKNSIRHNLSLHSKFIKVHNEATGKSSWWML
NPEGGKSGKAPRRRAASMDSSSKLLRGRSKAPKKKPSVLPAPPEGATPTSPVGHFAKWSG
SPCSRNREEADMWTTFRPRSSSNASSVSTRLSPLRPESEVLAEEIPASVSSYAGGVPPTL
NEGLELLDGLNLTSSHSLLSRSGLSGFSLQHPGVTGPLHTYSSSLFSPAEGPLSAGEGCF
SSSQALEALLTSDTPPPPADVLMTQVDPILSQAPTLLLLGGLPSSSKLATGVGLCPKPLE
APGPSSLVPTLSMIAPPPVMASAPIPKALGTPVLTPPTEAASQDRMPQDLDLDMYMENLE
CDMDNIISDLMDEGEGLDFNFEPDP

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Function
Transcription factor involved in the regulation of the insulin signaling pathway. Binds to insulin-response elements (IREs) and can activate transcription of IGFBP1. Down-regulates expression of HIF1A and suppresses hypoxia-induced transcriptional activation of HIF1A-modulated genes. Also involved in negative regulation of the cell cycle. Involved in increased proteasome activity in embryonic stem cells (ESCs) by activating expression of PSMD11 in ESCs, leading to enhanced assembly of the 26S proteasome, followed by higher proteasome activity.

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HGNC ID
HGNC:7139
KEGG ID hsa:4303
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
FOXO4 can regulate the following target(s), and cause disease/drug response(s). You can browse detail information of target(s) or disease/drug response(s).
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Browse Disease
NADPH oxidase 4 (NOX4) [Driver]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Driver
Responsed Disease Cardiomyopathy ICD-11: BC43
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model
 CHO-S/H9C2 cells Normal Cricetulus griseus CVCL_A0TS
Response regulation ENPP2 was transcriptionally regulated by FoxO4 to protect cardiomyocytes from Doxorubicininduced cardiotoxicity by inhibiting ferroptosis. In addition, the inhibitory effects of ENPP2 on Dox-induced ferroptosis were significantly reduced by FoxO4 overexpression, as demonstrated by increased Fe2+ and lipid ROS activity levels, decreased SLC7A11, GPX4 and FPN1 expression, and increased NOX4 expression, which were observed following FoxO4 overexpression.
Cardiomyopathy [ICD-11: BC43]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Forkhead box protein O4 (FOXO4) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model
 CHO-S/H9C2 cells Normal Cricetulus griseus CVCL_A0TS
Response regulation ENPP2 was transcriptionally regulated by FoxO4 to protect cardiomyocytes from Doxorubicininduced cardiotoxicity by inhibiting ferroptosis. In addition, the inhibitory effects of ENPP2 on Dox-induced ferroptosis were significantly reduced by FoxO4 overexpression, as demonstrated by increased Fe2+ and lipid ROS activity levels, decreased SLC7A11, GPX4 and FPN1 expression, and increased NOX4 expression, which were observed following FoxO4 overexpression.
References
Ref 1 Transcriptional activation of ENPP2 by FoxO4 protects cardiomyocytes from doxorubicininduced toxicity. Mol Med Rep. 2021 Sep;24(3):668. doi: 10.3892/mmr.2021.12307. Epub 2021 Jul 23.