Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10441)
Regulator Name Thioredoxin reductase 1, cytoplasmic (TXNRD1)
Synonyms
Gene associated with retinoic and interferon-induced mortality 12 protein; KM-102-derived reductase-like factor; Peroxidase TXNRD1; Thioredoxin reductase TR1
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Gene Name TXNRD1
Gene ID 7296
Regulator Type Protein coding
Uniprot ID Q16881
Sequence
MGCAEGKAVAAAAPTELQTKGKNGDGRRRSAKDHHPGKTLPENPAGFTSTATADSRALLQ
AYIDGHSVVIFSRSTCTRCTEVKKLFKSLCVPYFVLELDQTEDGRALEGTLSELAAETDL
PVVFVKQRKIGGHGPTLKAYQEGRLQKLLKMNGPEDLPKSYDYDLIIIGGGSGGLAAAKE
AAQYGKKVMVLDFVTPTPLGTRWGLGGTCVNVGCIPKKLMHQAALLGQALQDSRNYGWKV
EETVKHDWDRMIEAVQNHIGSLNWGYRVALREKKVVYENAYGQFIGPHRIKATNNKGKEK
IYSAERFLIATGERPRYLGIPGDKEYCISSDDLFSLPYCPGKTLVVGASYVALECAGFLA
GIGLDVTVMVRSILLRGFDQDMANKIGEHMEEHGIKFIRQFVPIKVEQIEAGTPGRLRVV
AQSTNSEEIIEGEYNTVMLAIGRDACTRKIGLETVGVKINEKTGKIPVTDEEQTNVPYIY
AIGDILEDKVELTPVAIQAGRLLAQRLYAGSTVKCDYENVPTTVFTPLEYGACGLSEEKA
VEKFGEENIEVYHSYFWPLEWTIPSRDNNKCYAKIICNTKDNERVVGFHVLGPNAGEVTQ
GFAAALKCGLTKKQLDSTIGIHPVCAEVFTTLSVTKRSGASILQAGCUG

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Family Class-I pyridine nucleotide-disulfide oxidoreductase family
Function
Reduces disulfideprotein thioredoxin (Trx) to its dithiol- containing form. Homodimeric flavoprotein involved in the regulation of cellular redox reactions, growth and differentiation. Contains a selenocysteine residue at the C-terminal active site that is essential for catalysis (Probable). Also has reductase activity on hydrogen peroxide (H2O2).; [Isoform 1]: Induces actin and tubulin polymerization, leading to formation of cell membrane protrusions.; [Isoform 4]: Enhances the transcriptional activity of estrogen receptors ESR1 and ESR2.; [Isoform 5]: Enhances the transcriptional activity of the estrogen receptor ESR2 only. Mediates cell death induced by a combination of interferon-beta and retinoic acid.

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HGNC ID
HGNC:12437
KEGG ID hsa:7296
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
TXNRD1 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).
Browse Target
Browse Disease
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Unspecific Target [Unspecific Target]
In total 3 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Responsed Disease Hemochromatosis ICD-11: 3B10-3B11
 Disease Info 
Responsed Drug Auranofin Investigative
 Drug Info 
Pathway Response JAK-STAT signaling pathway hsa04630
NF-kappa B signaling pathway hsa04064
Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
HEK-293T cells Normal Homo sapiens CVCL_0063
In Vivo Model
C57BL/6J mice (7-8 weeks of age, both males and females) were purchased from Vital River Laboratory Animal Technology Co., Ltd., Beijing, China. Hfe-/-mice were kindly provided by Dr. Nancy C. Andrews. All mice were housed in a specific pathogen-free facility and fed an egg white-based AIN-76A diet containing 50 mg/kg iron (Research Diets, Inc., New Brunswick, NJ).

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Response regulation High-dose auranofin (AUR) induces ferroptosis and causes lipid peroxidation through inhibition of thioredoxin reductase (TXNRD) activity.In conclusion, TXNRD is a key regulator of ferroptosis, and AUR is a novel activator of hepcidin and ferroptosis via distinct mechanisms, suggesting a promising approach for treating hemochromatosis and hepcidin-deficiency related disorders.
Experiment 2 Reporting the Ferroptosis Target of This Regulator [2]
Responsed Disease Chronic myeloid leukemia ICD-11: 2A20
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Glutathione metabolism hsa00480
Cell Process Cell ferroptosis
In Vitro Model
 K-562 cells Chronic myelogenous leukemia Homo sapiens CVCL_0004
K562/G01 cells Chronic myeloid leukemia Homo sapiens CVCL_4V47
Response regulation TXNRD1 is a key regulator involved in the ferroptosis of chronic myeloid leukemia cells induced by cysteine depletion in vitro. These findings highlight that cysteine depletion serves as a potential therapeutic strategy for overcoming chemotherapy resistance CML.
Experiment 3 Reporting the Ferroptosis Target of This Regulator [3]
Responsed Disease Melanoma ICD-11: 2C30
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model
 WM793 cells Melanoma Homo sapiens CVCL_8787
A2058 cells Amelanotic melanoma Homo sapiens CVCL_1059
A-375 cells Amelanotic melanoma Homo sapiens CVCL_0132
Hs 294T cells Melanoma Homo sapiens CVCL_0331
B16-F10 cells Melanoma Mus musculus CVCL_0159
In Vivo Model
In liproxstatin-1 rescue experiment, 5 x 105 B16F10 cells were subcutaneously injected into the right flank of C57BL/6 mice. When the tumor grows to 50 mm3, 100 ug anti-PD-1 antibody (Bio X Cell, USA), 30 mg/kg liproxstatin-1 (MedChemExpress, USA) or both were administered intraperitoneally to each mouse. Anti-PD-1 antibody was administered every 3 days and liproxstatin-1 was administered every day.

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Response regulation ATF3-induced miR-21-3p upregulation contributed to the efficacy of anti-PD-1 immunotherapy by facilitating melanoma cell ferroptosis via the suppression of the novel target TXNRD1 and lipid peroxidation. Nanoparticle delivery of miR-21-3p could sensitize melanoma cells to anti-PD-1 immunotherapy by facilitating ferroptosis.
Hemochromatosis [ICD-11: 3B10-3B11]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Thioredoxin reductase 1, cytoplasmic (TXNRD1) Protein coding
 Regulator Info 
Responsed Drug Auranofin Investigative
 Drug Info 
Pathway Response JAK-STAT signaling pathway hsa04630
NF-kappa B signaling pathway hsa04064
Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
HEK-293T cells Normal Homo sapiens CVCL_0063
In Vivo Model
C57BL/6J mice (7-8 weeks of age, both males and females) were purchased from Vital River Laboratory Animal Technology Co., Ltd., Beijing, China. Hfe-/-mice were kindly provided by Dr. Nancy C. Andrews. All mice were housed in a specific pathogen-free facility and fed an egg white-based AIN-76A diet containing 50 mg/kg iron (Research Diets, Inc., New Brunswick, NJ).

    Click to Show/Hide
Response regulation High-dose auranofin (AUR) induces ferroptosis and causes lipid peroxidation through inhibition of thioredoxin reductase (TXNRD) activity.In conclusion, TXNRD is a key regulator of ferroptosis, and AUR is a novel activator of hepcidin and ferroptosis via distinct mechanisms, suggesting a promising approach for treating hemochromatosis and hepcidin-deficiency related disorders.
Chronic myeloid leukemia [ICD-11: 2A20]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [2]
Target Regulator Thioredoxin reductase 1, cytoplasmic (TXNRD1) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Glutathione metabolism hsa00480
Cell Process Cell ferroptosis
In Vitro Model
 K-562 cells Chronic myelogenous leukemia Homo sapiens CVCL_0004
K562/G01 cells Chronic myeloid leukemia Homo sapiens CVCL_4V47
Response regulation TXNRD1 is a key regulator involved in the ferroptosis of chronic myeloid leukemia cells induced by cysteine depletion in vitro. These findings highlight that cysteine depletion serves as a potential therapeutic strategy for overcoming chemotherapy resistance CML.
Melanoma [ICD-11: 2C30]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [3]
Target Regulator Thioredoxin reductase 1, cytoplasmic (TXNRD1) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model
 WM793 cells Melanoma Homo sapiens CVCL_8787
A2058 cells Amelanotic melanoma Homo sapiens CVCL_1059
A-375 cells Amelanotic melanoma Homo sapiens CVCL_0132
Hs 294T cells Melanoma Homo sapiens CVCL_0331
B16-F10 cells Melanoma Mus musculus CVCL_0159
In Vivo Model
In liproxstatin-1 rescue experiment, 5 x 105 B16F10 cells were subcutaneously injected into the right flank of C57BL/6 mice. When the tumor grows to 50 mm3, 100 ug anti-PD-1 antibody (Bio X Cell, USA), 30 mg/kg liproxstatin-1 (MedChemExpress, USA) or both were administered intraperitoneally to each mouse. Anti-PD-1 antibody was administered every 3 days and liproxstatin-1 was administered every day.

    Click to Show/Hide
Response regulation ATF3-induced miR-21-3p upregulation contributed to the efficacy of anti-PD-1 immunotherapy by facilitating melanoma cell ferroptosis via the suppression of the novel target TXNRD1 and lipid peroxidation. Nanoparticle delivery of miR-21-3p could sensitize melanoma cells to anti-PD-1 immunotherapy by facilitating ferroptosis.
Auranofin [Investigative]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response [1]
Drug for Ferroptosis Inducer
Response Target Unspecific Target
Responsed Disease Hemochromatosis ICD-11: 3B10-3B11
 Disease Info 
Pathway Response JAK-STAT signaling pathway hsa04630
NF-kappa B signaling pathway hsa04064
Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
HEK-293T cells Normal Homo sapiens CVCL_0063
In Vivo Model
C57BL/6J mice (7-8 weeks of age, both males and females) were purchased from Vital River Laboratory Animal Technology Co., Ltd., Beijing, China. Hfe-/-mice were kindly provided by Dr. Nancy C. Andrews. All mice were housed in a specific pathogen-free facility and fed an egg white-based AIN-76A diet containing 50 mg/kg iron (Research Diets, Inc., New Brunswick, NJ).

    Click to Show/Hide
Response regulation High-dose auranofin (AUR) induces ferroptosis and causes lipid peroxidation through inhibition of thioredoxin reductase (TXNRD) activity.In conclusion, TXNRD is a key regulator of ferroptosis, and AUR is a novel activator of hepcidin and ferroptosis via distinct mechanisms, suggesting a promising approach for treating hemochromatosis and hepcidin-deficiency related disorders.
References
Ref 1 Auranofin mitigates systemic iron overload and induces ferroptosis via distinct mechanisms. Signal Transduct Target Ther. 2020 Jul 31;5(1):138. doi: 10.1038/s41392-020-00253-0.
Ref 2 TXNRD1: A Key Regulator Involved in the Ferroptosis of CML Cells Induced by Cysteine Depletion In Vitro. Oxid Med Cell Longev. 2021 Dec 7;2021:7674565. doi: 10.1155/2021/7674565. eCollection 2021.
Ref 3 Nanoparticle delivery of miR-21-3p sensitizes melanoma to anti-PD-1 immunotherapy by promoting ferroptosis. J Immunother Cancer. 2022 Jun;10(6):e004381. doi: 10.1136/jitc-2021-004381.