Ferroptosis Target Information

General Information of the Ferroptosis Target (ID: TAR10067)
Target Name Cytochrome b-245 heavy chain (CYBB)
Synonyms
NOX2; CGD91-phox; Cytochrome b(558) subunit beta (Cytochrome b558 subunit beta); Heme-binding membrane glycoprotein gp91phox; NADPH oxidase 2; Neutrophil cytochrome b 91 kDa polypeptide; Superoxide-generating NADPH oxidase heavy chain subunit; gp91-1; gp91-phox; p22 phagocyte B-cytochrome
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Gene Name CYBB
Sequence
MGNWAVNEGLSIFVILVWLGLNVFLFVWYYRVYDIPPKFFYTRKLLGSALALARAPAACL
NFNCMLILLPVCRNLLSFLRGSSACCSTRVRRQLDRNLTFHKMVAWMIALHSAIHTIAHL
FNVEWCVNARVNNSDPYSVALSELGDRQNESYLNFARKRIKNPEGGLYLAVTLLAGITGV
VITLCLILIITSSTKTIRRSYFEVFWYTHHLFVIFFIGLAIHGAERIVRGQTAESLAVHN
ITVCEQKISEWGKIKECPIPQFAGNPPMTWKWIVGPMFLYLCERLVRFWRSQQKVVITKV
VTHPFKTIELQMKKKGFKMEVGQYIFVKCPKVSKLEWHPFTLTSAPEEDFFSIHIRIVGD
WTEGLFNACGCDKQEFQDAWKLPKIAVDGPFGTASEDVFSYEVVMLVGAGIGVTPFASIL
KSVWYKYCNNATNLKLKKIYFYWLCRDTHAFEWFADLLQLLESQMQERNNAGFLSYNIYL
TGWDESQANHFAVHHDEEKDVITGLKQKTLYGRPNWDNEFKTIASQHPNTRIGVFLCGPE
ALAETLSKQSISNSESGPRGVHFIFNKENF

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Function
Critical component of the membrane-bound oxidase of phagocytes that generates superoxide. It is the terminal component of a respiratory chain that transfers single electrons from cytoplasmic NADPH across the plasma membrane to molecular oxygen on the exterior. Also functions as a voltage-gated proton channel that mediates the H+ currents of resting phagocytes. It participates in the regulation of cellular pH and is blocked by zinc.

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Gene ID 1536
Uniprot ID
P04839
Target Type Driver Suppressor Marker
Mechanism Diagram Click to View the Original Diagram
Full List of Regulator(s) of This Ferroptosis Target and Corresponding Disease/Drug Response(s)
CYBB can be involved in and affect the ferroptosis by the following regulators, and result in corresponding disease/drug response(s). You can browse corresponding disease or drug response(s) resulting from the regulation of certain regulators.
Browse Regulator related Disease
Browse Regulator related Drug
WW domain-containing transcription regulator protein 1 (WWTR1)
 Regulator Info 
Ovarian cancer [ICD-11: 2C73]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [1]
Regulator for Ferroptosis Driver
Responsed Drug Carboplatin Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Hippo signaling pathway hsa04390
Cell Process Cell ferroptosis
In Vitro Model
 Caov-2 cells Ovarian carcinoma Homo sapiens CVCL_6861
TOV-21G cells Ovarian clear cell adenocarcinoma Homo sapiens CVCL_3613
Response Description There is a significant correlation between the expression of ANGPTL4 and TAZ (encoded by WWTR1) in the TCGA ovarian tumor dataset. Carboplatin-treated CAOV2R cells are less sensitive to ferroptosis and have a lower level of TAZ (TAFAZZIN). TAZ promotes ferroptosis in ovarian cancers by regulating ANGPTL4 and NOX2, offering a novel therapeutic potential for ovarian tumors with TAZ activation.
Aquaporin-8 (AQP8)
 Regulator Info 
Cervical cancer [ICD-11: 2C77]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [2]
Regulator for Ferroptosis Driver
Responsed Drug Hydrogen Peroxide Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
SAS cells Tongue squamous cell carcinoma Homo sapiens CVCL_1675
Response Description Mitochondrial transfer upregulated the mitochondrial quality control protein prohibitin 2 (PHB2), which contributes to reduced AQPs(AQP3, AQP5, AQP8) expression. H2O2 treatment enhances AQPs expression, Fe2+ level, and lipid peroxidation, and decrease mitochondrial function by downregulating PHB2 in endocervical adenocarcinoma, and thus, is a promising modality for effective cancer treatment. Moreover, NOX2 expression is upregulated in 0 cells, and that NOX2 binds to AQP3, 5, and 8 in both HeLa and SAS cells.
Aquaporin-5 (AQP5)
 Regulator Info 
Cervical cancer [ICD-11: 2C77]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [2]
Regulator for Ferroptosis Driver
Responsed Drug Hydrogen Peroxide Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
SAS cells Tongue squamous cell carcinoma Homo sapiens CVCL_1675
Response Description Mitochondrial transfer upregulated the mitochondrial quality control protein prohibitin 2 (PHB2), which contributes to reduced AQPs(AQP3, AQP5,AQP8) expression. H2O2 treatment enhances AQPs expression, Fe2+ level, and lipid peroxidation, and decrease mitochondrial function by downregulating PHB2 in endocervical adenocarcinoma, and thus, is a promising modality for effective cancer treatment. Moreover, NOX2 expression is upregulated in 0 cells, and that NOX2 binds to AQP3, 5, and 8 in both HeLa and SAS cells.
Aquaporin-3 (AQP3)
 Regulator Info 
Cervical cancer [ICD-11: 2C77]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [2]
Regulator for Ferroptosis Driver
Responsed Drug Hydrogen Peroxide Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
SAS cells Tongue squamous cell carcinoma Homo sapiens CVCL_1675
Response Description Mitochondrial transfer upregulated the mitochondrial quality control protein prohibitin 2 (PHB2), which contributes to reduced AQPs( AQP3, AQP5,AQP8) expression. H2O2 treatment enhances AQPs expression, Fe2+ level, and lipid peroxidation, and decrease mitochondrial function by downregulating PHB2 in endocervical adenocarcinoma, and thus, is a promising modality for effective cancer treatment. Moreover, NOX2 expression is upregulated in 0 cells, and that NOX2 binds to AQP3, 5, and 8 in both HeLa and SAS cells.
Unspecific Regulator
Rhabdomyosarcoma [ICD-11: 2B55]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [3]
Responsed Drug Diphenyleneiodonium Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 RD cells Rhabdomyosarcoma Homo sapiens CVCL_1649
Rh18 cells Alveolar rhabdomyosarcoma Homo sapiens CVCL_1659
Rh30 cells Alveolar rhabdomyosarcoma Homo sapiens CVCL_0041
Rh36 cells Embryonal rhabdomyosarcoma Homo sapiens CVCL_M599
Rh41 cells Alveolar rhabdomyosarcoma Homo sapiens CVCL_2176
T 174 cells Rhabdomyosarcoma Homo sapiens CVCL_U955
TE 381.T cells Rhabdomyosarcoma Homo sapiens CVCL_1751
KYM-1 cells Embryonal rhabdomyosarcoma Homo sapiens CVCL_3007
Response Description Rhabdomyosarcoma (RMS) cells might be vulnerable to oxidative stress-induced cell death. The broad-spectrum protein kinase C (PKC) inhibitor Bisindolylmaleimide I as well as the PKC-a and b-selective inhibitor G6976 significantly reduced Erastin-induced cell death. Furthermore, the broad-spectrum nicotinamide adenine dinucleotide phosphate-oxidase (NOX, including NOX1, NOX2, NOX3, NOX4, NOX5, DUOX1 and DUOX2 inhibitor Diphenyleneiodonium and the selective NOX1/4 isoform inhibitor GKT137831 significantly decreased Erastin-stimulated ROS, lipid ROS and cell death.
Glioblastoma [ICD-11: 2A00]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [4]
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
Cell migration
Cell invasion
In Vitro Model
 U-87MG cells Glioblastoma Homo sapiens CVCL_GP63
In Vivo Model
A total of four groups were formed by randomly dividing the mice: control group consisting of shScramble xenografts treated with vehicle (n = 5), shScramble xenografts treated with IKE (n = 5), shSOD2 xenografts treated with vehicle (n = 5), and shSOD2 xenografts treated with IKE (n = 5). Drug treatment was started after the tumor volume reached approximately 100 mm3 or 10 days after the injection of the tumor xenograft. Depending on the treatment group, vehicles (5 mg/kg/day) or IKE (25 mg/kg/day) were administered intraperitoneally. Treatment was administered intraperitoneally for 3 weeks, and tumor growth was observed for 6 weeks after treatment began.

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Response Description CYBB captured ferroptosis resilience in mesenchymal glioblastoma multiforme (GBM). The downstream compensatory activity of CYBB via the Nrf2/SOD2 axis is exploitable through erastin-induced ferroptosis to overcome TMZ resistance.
WW domain-containing transcription regulator protein 1 (WWTR1)
 Regulator Info 
Carboplatin [Investigative]
In total 1 item(s) under this drug
 Drug Info 
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator [1]
Regulator for Ferroptosis Driver
Responsed Disease Ovarian cancer [ICD-11: 2C73]
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Hippo signaling pathway hsa04390
Cell Process Cell ferroptosis
In Vitro Model Caov-2 cells Ovarian carcinoma Homo sapiens CVCL_6861
TOV-21G cells Ovarian clear cell adenocarcinoma Homo sapiens CVCL_3613
Response Description There is a significant correlation between the expression of ANGPTL4 and TAZ (encoded by WWTR1) in the TCGA ovarian tumor dataset. Carboplatin-treated CAOV2R cells are less sensitive to ferroptosis and have a lower level of TAZ (TAFAZZIN). TAZ promotes ferroptosis in ovarian cancers by regulating ANGPTL4 and NOX2, offering a novel therapeutic potential for ovarian tumors with TAZ activation.
Aquaporin-8 (AQP8)
 Regulator Info 
Hydrogen Peroxide [Investigative]
In total 1 item(s) under this drug
 Drug Info 
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator [2]
Regulator for Ferroptosis Driver
Responsed Disease Cervical cancer [ICD-11: 2C77]
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
SAS cells Tongue squamous cell carcinoma Homo sapiens CVCL_1675
Response Description Mitochondrial transfer upregulated the mitochondrial quality control protein prohibitin 2 (PHB2), which contributes to reduced AQPs(AQP3, AQP5, AQP8) expression. H2O2 treatment enhances AQPs expression, Fe2+ level, and lipid peroxidation, and decrease mitochondrial function by downregulating PHB2 in endocervical adenocarcinoma, and thus, is a promising modality for effective cancer treatment. Moreover, NOX2 expression is upregulated in 0 cells, and that NOX2 binds to AQP3, 5, and 8 in both HeLa and SAS cells.
Aquaporin-5 (AQP5)
 Regulator Info 
Hydrogen Peroxide [Investigative]
In total 1 item(s) under this drug
 Drug Info 
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator [2]
Regulator for Ferroptosis Driver
Responsed Disease Cervical cancer [ICD-11: 2C77]
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
SAS cells Tongue squamous cell carcinoma Homo sapiens CVCL_1675
Response Description Mitochondrial transfer upregulated the mitochondrial quality control protein prohibitin 2 (PHB2), which contributes to reduced AQPs(AQP3, AQP5,AQP8) expression. H2O2 treatment enhances AQPs expression, Fe2+ level, and lipid peroxidation, and decrease mitochondrial function by downregulating PHB2 in endocervical adenocarcinoma, and thus, is a promising modality for effective cancer treatment. Moreover, NOX2 expression is upregulated in 0 cells, and that NOX2 binds to AQP3, 5, and 8 in both HeLa and SAS cells.
Aquaporin-3 (AQP3)
 Regulator Info 
Hydrogen Peroxide [Investigative]
In total 1 item(s) under this drug
 Drug Info 
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator [2]
Regulator for Ferroptosis Driver
Responsed Disease Cervical cancer [ICD-11: 2C77]
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
SAS cells Tongue squamous cell carcinoma Homo sapiens CVCL_1675
Response Description Mitochondrial transfer upregulated the mitochondrial quality control protein prohibitin 2 (PHB2), which contributes to reduced AQPs( AQP3, AQP5,AQP8) expression. H2O2 treatment enhances AQPs expression, Fe2+ level, and lipid peroxidation, and decrease mitochondrial function by downregulating PHB2 in endocervical adenocarcinoma, and thus, is a promising modality for effective cancer treatment. Moreover, NOX2 expression is upregulated in 0 cells, and that NOX2 binds to AQP3, 5, and 8 in both HeLa and SAS cells.
Unspecific Regulator
Diphenyleneiodonium [Investigative]
In total 1 item(s) under this drug
 Drug Info 
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator [3]
Responsed Disease Rhabdomyosarcoma [ICD-11: 2B55]
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model RD cells Rhabdomyosarcoma Homo sapiens CVCL_1649
Rh18 cells Alveolar rhabdomyosarcoma Homo sapiens CVCL_1659
Rh30 cells Alveolar rhabdomyosarcoma Homo sapiens CVCL_0041
Rh36 cells Embryonal rhabdomyosarcoma Homo sapiens CVCL_M599
Rh41 cells Alveolar rhabdomyosarcoma Homo sapiens CVCL_2176
T 174 cells Rhabdomyosarcoma Homo sapiens CVCL_U955
TE 381.T cells Rhabdomyosarcoma Homo sapiens CVCL_1751
KYM-1 cells Embryonal rhabdomyosarcoma Homo sapiens CVCL_3007
Response Description Rhabdomyosarcoma (RMS) cells might be vulnerable to oxidative stress-induced cell death. The broad-spectrum protein kinase C (PKC) inhibitor Bisindolylmaleimide I as well as the PKC-a and b-selective inhibitor G6976 significantly reduced Erastin-induced cell death. Furthermore, the broad-spectrum nicotinamide adenine dinucleotide phosphate-oxidase (NOX, including NOX1, NOX2, NOX3, NOX4, NOX5, DUOX1 and DUOX2 inhibitor Diphenyleneiodonium and the selective NOX1/4 isoform inhibitor GKT137831 significantly decreased Erastin-stimulated ROS, lipid ROS and cell death.
References
Ref 1 A TAZ-ANGPTL4-NOX2 Axis Regulates Ferroptotic Cell Death and Chemoresistance in Epithelial Ovarian Cancer. Mol Cancer Res. 2020 Jan;18(1):79-90. doi: 10.1158/1541-7786.MCR-19-0691. Epub 2019 Oct 22.
Ref 2 Mitochondrial dysfunction promotes aquaporin expression that controls hydrogen peroxide permeability and ferroptosis. Free Radic Biol Med. 2020 Dec;161:60-70. doi: 10.1016/j.freeradbiomed.2020.09.027. Epub 2020 Oct 2.
Ref 3 Targeting ferroptosis in rhabdomyosarcoma cells. Int J Cancer. 2020 Jan 15;146(2):510-520. doi: 10.1002/ijc.32496. Epub 2019 Jul 4.
Ref 4 NADPH Oxidase Subunit CYBB Confers Chemotherapy and Ferroptosis Resistance in Mesenchymal Glioblastoma via Nrf2/SOD2 Modulation. Int J Mol Sci. 2023 Apr 22;24(9):7706. doi: 10.3390/ijms24097706.